Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Lymphatic Metastasis in the Absence of Functional Intratumor Lymphatics
Timothy P. Padera,1Ananth Kadambi,1*Emmanuelle di Tomaso,1Carla Mouta Carreira,1Edward B. Brown,1Yves Boucher,1Noah C. Choi,1Douglas Mathisen,2John Wain,2Eugene J. Mark,3Lance L. Munn,1Rakesh K. Jain1
Lymphatic metastasis contributes to mortality from solid tumors.
Whether metastasizing cancer cells reach lymph nodes viaintratumor
lymphatic vessels is unknown. Here, we examine functionallymphatics
associated with mouse tumors expressing normal or elevatedlevels of
vascular endothelial growth factor-C (VEGF-C), a
moleculethat stimulates lymphangiogenesis. Although VEGF-C
overexpressionincreased lymphatic surface area in the tumor margin and
lymphaticmetastasis, these tumors contained no functional lymphatics,
asassessed by four independent functional assays and
immunohistochemicalstaining. These findings suggest that the
functional lymphaticsin the tumor margin alone are sufficient for
lymphatic metastasisand should be targeted therapeutically.
1 E. L. Steele Laboratory, Department of
Radiation Oncology,
2 Department of Surgery,
3 Department of Pathology, Massachusetts General
Hospital, Harvard Medical School, 100 Blossom Street, Boston, MA 02114, USA.
*
Present address: Comprehensive Cancer Center, University of
California-San Francisco, 2340 Sutter Street, N461, San Francisco,CA
94143-0808, USA.
Present address: Center for Molecular Medicine, Maine
Medical Center Research Institute, 81 Research Drive, Scarborough, ME04074, USA.
To whom correspondence should be addressed. E-mail:
jain{at}steele.mgh.harvard.edu
The editors suggest the following Related Resources on Science sites:
In Science Magazine
PERSPECTIVES
Jeffrey E. Gershenwald and Isaiah J. Fidler (7 June 2002) Science296 (5574), 1811.
[DOI: 10.1126/science.10731318] |Summary »|Full Text »|PDF »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Intraocular Lymphangiogenesis in Malignant Melanomas of the Ciliary Body with Extraocular Extension.
L. M. Heindl, T. N. Hofmann, H. L. J. Knorr, C. Rummelt, F. Schrodl, U. Schlotzer-Schrehardt, L. M. Holbach, G. O. H. Naumann, F. E. Kruse, and C. Cursiefen (2009)
Invest. Ophthalmol. Vis. Sci.
50, 1988-1995
|Abstract »|Full Text »|PDF »
Lymphatic Vessel Density in Correlation to Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma.
S. FRECH, K. HORMANN, F. RIEDEL, and K. GOTTE (2009)
Anticancer Res
29, 1675-1679
|Abstract »|Full Text »|PDF »
Increased Vascular Endothelial Growth Factor-C Expression Is Insufficient to Induce Lymphatic Metastasis in Human Soft-Tissue Sarcomas.
G. Lahat, A. Lazar, X. Wang, W.-L. Wang, Q.-S. Zhu, K. K. Hunt, R. E. Pollock, and D. Lev (2009)
Clin. Cancer Res.
15, 2637-2646
|Abstract »|Full Text »|PDF »
Endothelial Nitric Oxide Synthase Mediates Lymphangiogenesis and Lymphatic Metastasis.
J. Lahdenranta, J. Hagendoorn, T. P. Padera, T. Hoshida, G. Nelson, S. Kashiwagi, R. K. Jain, and D. Fukumura (2009)
Cancer Res.
69, 2801-2808
|Abstract »|Full Text »|PDF »
Lymphovascular Invasion Predicts Clinical Outcomes in Patients With Node-Negative Upper Tract Urothelial Carcinoma.
E. Kikuchi, V. Margulis, P. I. Karakiewicz, M. Roscigno, S. Mikami, Y. Lotan, M. Remzi, C. Bolenz, C. Langner, A. Weizer, et al. (2009)
J. Clin. Oncol.
27, 612-618
|Abstract »|Full Text »|PDF »
Lymphangiogenesis in Esophageal Adenocarcinomas--Lymphatic Vessel Density as Prognostic Marker in Esophageal Adenocarcinoma.
R. S. Saad, J. L. Lindner, Y. Liu, and J. F. Silverman (2009)
Am J Clin Pathol
131, 92-98
|Abstract »|Full Text »|PDF »
Vascular Endothelial Growth Factor-C and C-C Chemokine Receptor 7 in Tumor Cell-Lymphatic Cross-talk Promote Invasive Phenotype.
A. Issa, T. X. Le, A. N. Shoushtari, J. D. Shields, and M. A. Swartz (2009)
Cancer Res.
69, 349-357
|Abstract »|Full Text »|PDF »
Suppression of Prostate Cancer Nodal and Systemic Metastasis by Blockade of the Lymphangiogenic Axis.
J. B. Burton, S. J. Priceman, J. L. Sung, E. Brakenhielm, D. S. An, B. Pytowski, K. Alitalo, and L. Wu (2008)
Cancer Res.
68, 7828-7837
|Abstract »|Full Text »|PDF »
Differential response of primary tumor versus lymphatic metastasis to VEGFR-2 and VEGFR-3 kinase inhibitors cediranib and vandetanib.
T. P. Padera, A. H. Kuo, T. Hoshida, S. Liao, J. Lobo, K. R. Kozak, D. Fukumura, and R. K. Jain (2008)
Mol. Cancer Ther.
7, 2272-2279
|Abstract »|Full Text »|PDF »
Metinel Node--The First Lymph Node Draining a Metastasis--Contains Tumor-Reactive Lymphocytes.
K. Dahl, M. Karlsson, P. Marits, A. Hoffstedt, O. Winqvist, and M. Thorn (2008)
Ann. Surg. Oncol.
15, 1454-1463
|Abstract »|Full Text »|PDF »
Pituitary Tumor-Transforming 1 Increases Cell Motility and Promotes Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma.
T. Ito, Y. Shimada, T. Kan, S. David, Y. Cheng, Y. Mori, R. Agarwal, B. Paun, Z. Jin, A. Olaru, et al. (2008)
Cancer Res.
68, 3214-3224
|Abstract »|Full Text »|PDF »
Distributions of Angiogenesis and Lymphangiogenesis in Gastrointestinal Intramucosal Tumors.
Y. Gao, W.-X. Zhong, D.-B. Mu, Y.-P. Yuan, Y.-H. Zhang, J.-M. Yu, L.-P. Sun, L. Wang, Y.-H. Li, J.-B. Zhang, et al. (2008)
Ann. Surg. Oncol.
15, 1117-1123
|Abstract »|Full Text »|PDF »
Tumor-Associated Lymphangiogenesis Correlates with Lymph Node Metastases and Prognosis in Hilar Cholangiocarcinoma.
A. Thelen, A. Scholz, C. Benckert, W. Weichert, E. Dietz, B. Wiedenmann, P. Neuhaus, and S. Jonas (2008)
Ann. Surg. Oncol.
15, 791-799
|Abstract »|Full Text »|PDF »
Inhibition of Multiple Vascular Endothelial Growth Factor Receptors (VEGFR) Blocks Lymph Node Metastases but Inhibition of VEGFR-2 Is Sufficient to Sensitize Tumor Cells to Platinum-Based Chemotherapeutics.
P. Sini, I. Samarzija, F. Baffert, A. Littlewood-Evans, C. Schnell, A. Theuer, S. Christian, A. Boos, H. Hess-Stumpp, J. A. Foekens, et al. (2008)
Cancer Res.
68, 1581-1592
|Abstract »|Full Text »|PDF »
VEGF-C is associated with lymphatic status and invasion in oral cancer.
B S M S Siriwardena, Y Kudo, I Ogawa, M N G P K Udagama, W M Tilakaratne, and T Takata (2008)
J. Clin. Pathol.
61, 103-108
|Abstract »|Full Text »|PDF »
Significance of Tumor-Associated Stroma in Promotion of Intratumoral Lymphangiogenesis: Pivotal Role of a Hyaluronan-Rich Tumor Microenvironment.
H. Koyama, N. Kobayashi, M. Harada, M. Takeoka, Y. Kawai, K. Sano, M. Fujimori, J. Amano, T. Ohhashi, R. Kannagi, et al. (2008)
Am. J. Pathol.
172, 179-193
|Abstract »|Full Text »|PDF »
Real-time Imaging of Tumor-Cell Shedding and Trafficking in Lymphatic Channels.
K. Hayashi, P. Jiang, K. Yamauchi, N. Yamamoto, H. Tsuchiya, K. Tomita, A.R. Moossa, M. Bouvet, and R. M. Hoffman (2007)
Cancer Res.
67, 8223-8228
|Abstract »|Full Text »|PDF »
Lymphatic vascular density and lymphangiogenesis during tumour progression of carcinoma ex pleomorphic adenoma.
A B Soares, L Ponchio, P B Juliano, V C de Araujo, and A Altemani (2007)
J. Clin. Pathol.
60, 995-1000
|Abstract »|Full Text »|PDF »
Toward a Systems Engineering Approach to Cancer Drug Delivery.
M. R. Dreher and A. Chilkoti (2007)
J Natl Cancer Inst
99, 983-985
|Full Text »|PDF »
Vascular endothelial growth factor-C stimulates the lymphatic pump by a VEGF receptor-3-dependent mechanism.
J. W. Breslin, N. Gaudreault, K. D. Watson, R. Reynoso, S. Y. Yuan, and M. H. Wu (2007)
Am J Physiol Heart Circ Physiol
293, H709-H718
|Abstract »|Full Text »|PDF »
Distinctive Features of Angiogenesis and Lymphangiogenesis Determine Their Functionality during De novo Tumor Development.
A. Eichten, W. C. Hyun, and L. M. Coussens (2007)
Cancer Res.
67, 5211-5220
|Abstract »|Full Text »|PDF »
Effect of Vascular Normalization by Antiangiogenic Therapy on Interstitial Hypertension, Peritumor Edema, and Lymphatic Metastasis: Insights from a Mathematical Model.
M. I. Harrell, B. M. Iritani, and A. Ruddell (2007)
Am. J. Pathol.
170, 774-786
|Abstract »|Full Text »|PDF »
Vascular Endothelial Growth Factor Receptor 3 Is Involved in Tumor Angiogenesis and Growth.
P. Laakkonen, M. Waltari, T. Holopainen, T. Takahashi, B. Pytowski, P. Steiner, D. Hicklin, K. Persaud, J. R. Tonra, L. Witte, et al. (2007)
Cancer Res.
67, 593-599
|Abstract »|Full Text »|PDF »
Intratumoral Lymphatic Vessels and VEGF-C Expression Are Predictive Factors of Lymph Node Relapse in T1-T4 N0 Laryngopharyngeal Squamous Cell Carcinoma.
A. Hinojar-Gutierrez, M.-E. Fernandez-Contreras, R. Gonzalez-Gonzalez, M.-J. Fernandez-Luque, A. Hinojar-Arzadun, M. Quintanilla, and C. Gamallo (2007)
Ann. Surg. Oncol.
14, 248-257
|Abstract »|Full Text »|PDF »
Tumor Cell Transendothelial Passage in the Absorbing Lymphatic Vessel of Transgenic Adenocarcinoma Mouse Prostate.
Tumor-Induced Activation of Lymphatic Endothelial Cells via Vascular Endothelial Growth Factor Receptor-2 Is Critical for Prostate Cancer Lymphatic Metastasis.
Y. Zeng, K. Opeskin, J. Goad, and E. D. Williams (2006)
Cancer Res.
66, 9566-9575
|Abstract »|Full Text »|PDF »
Tumor and lymph node lymphangiogenesis--impact on cancer metastasis.
Allometric Scaling Law Questions the Traditional Mechanical Model for Axillary Lymph Node Involvement in Breast Cancer.
R. Demicheli, E. Biganzoli, P. Boracchi, M. Greco, W. J.M. Hrushesky, and M. W. Retsky (2006)
J. Clin. Oncol.
24, 4391-4396
|Abstract »|Full Text »|PDF »
Estrogen receptor positive breast cancer metastasis: altered hormonal sensitivity and tumor aggressiveness in lymphatic vessels and lymph nodes..
J. C. Harrell, W. W. Dye, D. C. Allred, P. Jedlicka, N. S. Spoelstra, C. A. Sartorius, and K. B. Horwitz (2006)
Cancer Res.
66, 9308-9315
|Abstract »|Full Text »|PDF »
Lymphatic vessels in cancer metastasis: bridging the gaps.
R. Shayan, M. G. Achen, and S. A. Stacker (2006)
Carcinogenesis
27, 1729-1738
|Abstract »|Full Text »|PDF »
Imaging Steps of Lymphatic Metastasis Reveals That Vascular Endothelial Growth Factor-C Increases Metastasis by Increasing Delivery of Cancer Cells to Lymph Nodes: Therapeutic Implications.
T. Hoshida, N. Isaka, J. Hagendoorn, E. di Tomaso, Y.-L. Chen, B. Pytowski, D. Fukumura, T. P. Padera, and R. K. Jain (2006)
Cancer Res.
66, 8065-8075
|Abstract »|Full Text »|PDF »
Lymphatic Zip Codes in Premalignant Lesions and Tumors.
L. Zhang, E. Giraudo, J. A. Hoffman, D. Hanahan, and E. Ruoslahti (2006)
Cancer Res.
66, 5696-5706
|Abstract »|Full Text »|PDF »
Onset of abnormal blood and lymphatic vessel function and interstitial hypertension in early stages of carcinogenesis..
J. Hagendoorn, R. Tong, D. Fukumura, Q. Lin, J. Lobo, T. P. Padera, L. Xu, R. Kucherlapati, and R. K. Jain (2006)
Cancer Res.
66, 3360-3364
|Abstract »|Full Text »|PDF »
Results of Initial Operations in Non-Small Cell Lung Cancer Patients With Single-Level N2 Disease.
Y. Ohta, Y. Shimizu, H. Minato, I. Matsumoto, M. Oda, and G. Watanabe (2006)
Ann. Thorac. Surg.
81, 427-433
|Abstract »|Full Text »|PDF »
Overcoming Physiologic Barriers to Cancer Treatment by Molecularly Targeting the Tumor Microenvironment.
Tumour lymphangiogenesis is a possible predictor of sentinel lymph node status in cutaneous melanoma: a case-control study.
D Massi, S Puig, A Franchi, J Malvehy, S Vidal-Sicart, M Gonzalez-Cao, G Baroni, S Ketabchi, J Palou, and M Santucci (2006)
J. Clin. Pathol.
59, 166-173
|Abstract »|Full Text »|PDF »
Lymphatic vessel density in the neoplastic progression of Barrett's oesophagus to adenocarcinoma.
M-A Brundler, J A Harrison, B de Saussure, M de Perrot, and M S Pepper (2006)
J. Clin. Pathol.
59, 191-195
|Abstract »|Full Text »|PDF »
Vascular Endothelial Growth Factor-D and Its Receptor VEGFR-3: Two Novel Independent Prognostic Markers in Gastric Adenocarcinoma.
S. Juttner, C. Wissmann, T. Jons, M. Vieth, J. Hertel, S. Gretschel, P. M. Schlag, W. Kemmner, and M. Hocker (2006)
J. Clin. Oncol.
24, 228-240
|Abstract »|Full Text »|PDF »
Peritumoral Lymphatic Vessel Density and Vascular Endothelial Growth Factor C Expression in Early-Stage Squamous Cell Carcinoma of the Uterine Cervix.
Z. Gombos, X. Xu, C. S. Chu, P. J. Zhang, and G. Acs (2005)
Clin. Cancer Res.
11, 8364-8371
|Abstract »|Full Text »|PDF »
Increased Expression of Vascular Endothelial Growth Factor C in Papillary Thyroid Carcinoma Correlates with Cervical Lymph Node Metastases.
X.-M. Yu, C.-Y. Lo, W.-F. Chan, K.-Y. Lam, P. Leung, and J. M. Luk (2005)
Clin. Cancer Res.
11, 8063-8069
|Abstract »|Full Text »|PDF »
Tumor-Secreted Vascular Endothelial Growth Factor-C Is Necessary for Prostate Cancer Lymphangiogenesis, but Lymphangiogenesis Is Unnecessary for Lymph Node Metastasis.
S. Y. Wong, H. Haack, D. Crowley, M. Barry, R. T. Bronson, and R. O. Hynes (2005)
Cancer Res.
65, 9789-9798
|Abstract »|Full Text »|PDF »
Vascular Endothelial Growth Factor-A Promotes Peritumoral Lymphangiogenesis and Lymphatic Metastasis.
M. A. Bjorndahl, R. Cao, J. B. Burton, E. Brakenhielm, P. Religa, D. Galter, L. Wu, and Y. Cao (2005)
Cancer Res.
65, 9261-9268
|Abstract »|Full Text »|PDF »
Lymphangiogenesis Correlates with Lymph Node Metastasis, Prognosis, and Angiogenic Phenotype in Human Non-Small Cell Lung Cancer.
F. Renyi-Vamos, J. Tovari, J. Fillinger, J. Timar, S. Paku, I. Kenessey, G. Ostoros, L. Agocs, I. Soltesz, and B. Dome (2005)
Clin. Cancer Res.
11, 7344-7353
|Abstract »|Full Text »|PDF »
Volumetric MR Imaging of Oral, Maxillary Sinus, Oropharyngeal, and Hypopharyngeal Cancers: Correlation between Tumor Volume and Lymph Node Metastasis.
Y. Kimura, M. Sumi, Y. Ichikawa, Y. Kawai, and T. Nakamura (2005)
AJNR Am. J. Neuroradiol.
26, 2384-2389
|Abstract »|Full Text »|PDF »
Down-Regulation of Vascular Endothelial Cell Growth Factor-C Expression Using Small Interfering RNA Vectors in Mammary Tumors Inhibits Tumor Lymphangiogenesis and Spontaneous Metastasis and Enhances Survival.
Z. Chen, M. L. Varney, M. W. Backora, K. Cowan, J. C. Solheim, J. E. Talmadge, and R. K. Singh (2005)
Cancer Res.
65, 9004-9011
|Abstract »|Full Text »|PDF »
64Cu-Labeled Folate-Conjugated Shell Cross-Linked Nanoparticles for Tumor Imaging and Radiotherapy: Synthesis, Radiolabeling, and Biologic Evaluation.
R. Rossin, D. Pan, K. Qi, J. L. Turner, X. Sun, K. L. Wooley, and M. J. Welch (2005)
J. Nucl. Med.
46, 1210-1218
|Abstract »|Full Text »|PDF »
AZD2171: A Highly Potent, Orally Bioavailable, Vascular Endothelial Growth Factor Receptor-2 Tyrosine Kinase Inhibitor for the Treatment of Cancer.
S. R. Wedge, J. Kendrew, L. F. Hennequin, P. J. Valentine, S. T. Barry, S. R. Brave, N. R. Smith, N. H. James, M. Dukes, J. O. Curwen, et al. (2005)
Cancer Res.
65, 4389-4400
|Abstract »|Full Text »|PDF »
Detection of Lymphatic Invasion in Primary Melanoma With Monoclonal Antibody D2-40: A New Selective Immunohistochemical Marker of Lymphatic Endothelium.
F. Niakosari, H. J. Kahn, A. Marks, and L. From (2005)
Arch Dermatol
141, 440-444
|Abstract »|Full Text »|PDF »
Interstitial Transport in Tumors: Barriers and Strategies for Improvement.
R. K. Jain (2005)
Am. Assoc. Cancer Res. Educ. Book
2005, 108-113
|Full Text »|PDF »
Characterizing Extravascular Fluid Transport of Macromolecules in the Tumor Interstitium by Magnetic Resonance Imaging.
A. P. Pathak, D. Artemov, B. D. Ward, D. G. Jackson, M. Neeman, and Z. M. Bhujwalla (2005)
Cancer Res.
65, 1425-1432
|Abstract »|Full Text »|PDF »
The biology of vascular endothelial growth factors.
T. Tammela, B. Enholm, K. Alitalo, and K. Paavonen (2005)
Cardiovasc Res
65, 550-563
|Abstract »|Full Text »|PDF »
Prognostic Implications of Multiple Lymphatic Basin Drainage in Patients With Truncal Melanoma.
R. E. Jimenez, K. Panageas, K. J. Busam, and M. S. Brady (2005)
J. Clin. Oncol.
23, 518-524
|Abstract »|Full Text »|PDF »
Complete and Specific Inhibition of Adult Lymphatic Regeneration by a Novel VEGFR-3 Neutralizing Antibody.
B. Pytowski, J. Goldman, K. Persaud, Y. Wu, L. Witte, D. J. Hicklin, M. Skobe, K. C. Boardman, and M. A. Swartz (2005)
J Natl Cancer Inst
97, 14-21
|Abstract »|Full Text »|PDF »
Impact of Vascular Endothelial Growth Factor-C and -D Expression in Human Pancreatic Cancer: Its Relationship to Lymph Node Metastasis.
H. Kurahara, S. Takao, K. Maemura, H. Shinchi, S. Natsugoe, and T. Aikou (2004)
Clin. Cancer Res.
10, 8413-8420
|Abstract »|Full Text »|PDF »
High LYVE-1-Positive Lymphatic Vessel Numbers Are Associated with Poor Outcome in Breast Cancer.
P. Bono, V.-M. Wasenius, P. Heikkila, J. Lundin, D. G. Jackson, and H. Joensuu (2004)
Clin. Cancer Res.
10, 7144-7149
|Abstract »|Full Text »|PDF »
Physiological characterization of human ovarian cancer cells in a rat model of intraperitoneal antineoplastic therapy.
M. F. Flessner, J. Choi, Z. He, and K. Credit (2004)
J Appl Physiol
97, 1518-1526
|Abstract »|Full Text »|PDF »
In Vivo Flow Cytometry: A New Method for Enumerating Circulating Cancer Cells.
I. Georgakoudi, N. Solban, J. Novak, W. L. Rice, X. Wei, T. Hasan, and C. P. Lin (2004)
Cancer Res.
64, 5044-5047
|Abstract »|Full Text »|PDF »
N. Isaka, T. P. Padera, J. Hagendoorn, D. Fukumura, and R. K. Jain (2004)
Cancer Res.
64, 4400-4404
|Abstract »|Full Text »|PDF »
Lack of lymphangiogenesis during breast carcinogenesis.
M M Vleugel, R Bos, P van der Groep, A E Greijer, A Shvarts, H V Stel, E van der Wall, and P J van Diest (2004)
J. Clin. Pathol.
57, 746-751
|Abstract »|Full Text »|PDF »
Activation of Vascular Endothelial Growth Factor Receptor-3 and Its Downstream Signaling Promote Cell Survival under Oxidative Stress.
J. F. Wang, X. Zhang, and J. E. Groopman (2004)
J. Biol. Chem.
279, 27088-27097
|Abstract »|Full Text »|PDF »
Vascular Normalization by Vascular Endothelial Growth Factor Receptor 2 Blockade Induces a Pressure Gradient Across the Vasculature and Improves Drug Penetration in Tumors.
R. T. Tong, Y. Boucher, S. V. Kozin, F. Winkler, D. J. Hicklin, and R. K. Jain (2004)
Cancer Res.
64, 3731-3736
|Abstract »|Full Text »|PDF »
Preexisting Lymphatic Endothelium but not Endothelial Progenitor Cells Are Essential for Tumor Lymphangiogenesis and Lymphatic Metastasis.
Y. He, I. Rajantie, M. Ilmonen, T. Makinen, M. J. Karkkainen, P. Haiko, P. Salven, and K. Alitalo (2004)
Cancer Res.
64, 3737-3740
|Abstract »|Full Text »|PDF »
Demonstration of altered signaling responses in bone marrow extracellular fluid during increased hematopoiesis in rats using a centrifugation method.
H. Wiig, E. Berggreen, B. A. S. Borge, and P. O. Iversen (2004)
Am J Physiol Heart Circ Physiol
286, H2028-H2034
|Abstract »|Full Text »|PDF »
Acute Hypoxia Enhances Spontaneous Lymph Node Metastasis in an Orthotopic Murine Model of Human Cervical Carcinoma.
Correspondence re: S. Maula et al., Intratumoral Lymphatics Are Essential for the Metastatic Spread and Prognosis in Squamous Cell Carcinoma of the Head and Neck. Cancer Res., 63: 1920-1926, 2003..
T. P. Padera, Y. Boucher, R. K. Jain, L. M. Wein, P. E. Holden, and D. H. Kirn (2003)
Cancer Res.
63, 8555-8557
|Full Text »|PDF »
Reply.
S.-M. Maula, S. Jalkanen, R. Ristamaki, D. Jackson, R. Grenman, and M. Luukkaa (2003)
Cancer Res.
63, 8558
|Full Text »|PDF »
Gene Expression Profiling in Clinically Localized Prostate Cancer: A Four-Gene Expression Model Predicts Clinical Behavior.
A. Latil, I. Bieche, L. Chene, I. Laurendeau, P. Berthon, O. Cussenot, and M. Vidaud (2003)
Clin. Cancer Res.
9, 5477-5485
|Abstract »|Full Text »|PDF »
Lymphatic endothelium: morphological, molecular and functional properties.
Perspectives and Risks of Breast-Conservation Therapy for Breast Cancer.
D. H. Roukos, A. M. Kappas, and N. J. Agnantis (2003)
Ann. Surg. Oncol.
10, 718-721
|Full Text »|PDF »
Mannose Receptor (MR) and Common Lymphatic Endothelial and Vascular Endothelial Receptor (CLEVER)-1 Direct the Binding of Cancer Cells to the Lymph Vessel Endothelium.
H. Irjala, K. Alanen, R. Grenman, P. Heikkila, H. Joensuu, and S. Jalkanen (2003)
Cancer Res.
63, 4671-4676
|Abstract »|Full Text »|PDF »
Tumor Lymphangiogenesis: A Novel Prognostic Indicator for Cutaneous Melanoma Metastasis and Survival.
S. S. Dadras, T. Paul, J. Bertoncini, L. F. Brown, A. Muzikansky, D. G. Jackson, U. Ellwanger, C. Garbe, M. C. Mihm, and M. Detmar (2003)
Am. J. Pathol.
162, 1951-1960
|Abstract »|Full Text »|PDF »
Intratumoral Lymphatics Are Essential for the Metastatic Spread and Prognosis in Squamous Cell Carcinomas of the Head and Neck Region.
S.-M. Maula, M. Luukkaa, R. Grenman, D. Jackson, S. Jalkanen, and R. Ristamaki (2003)
Cancer Res.
63, 1920-1926
|Abstract »|Full Text »|PDF »
Vascular Endothelial Growth Factor C Expression and Lymph Node Metastasis Are Regulated by the Type I Insulin-like Growth Factor Receptor.
Y. Tang, D. Zhang, L. Fallavollita, and P. Brodt (2003)
Cancer Res.
63, 1166-1171
|Abstract »|Full Text »|PDF »
Differential in Vivo and in Vitro Expression of Vascular Endothelial Growth Factor (VEGF)-C and VEGF-D in Tumors and Its Relationship to Lymphatic Metastasis in Immunocompetent Rats.
J. Krishnan, V. Kirkin, A. Steffen, M. Hegen, D. Weih, S. Tomarev, J. Wilting, and J. P. Sleeman (2003)
Cancer Res.
63, 713-722
|Abstract »|Full Text »|PDF »
Micro-magnetic Resonance Lymphangiography in Mice Using a Novel Dendrimer-based Magnetic Resonance Imaging Contrast Agent.
H. Kobayashi, S. Kawamoto, R. A. Star, T. A. Waldmann, Y. Tagaya, and M. W. Brechbiel (2003)
Cancer Res.
63, 271-276
|Abstract »|Full Text »|PDF »
Independent Prognostic Impact of Lymphatic Vessel Density and Presence of Low-Grade Lymphangiogenesis in Cutaneous Melanoma.
O. Straume, D. G. Jackson, and L. A. Akslen (2003)
Clin. Cancer Res.
9, 250-256
|Abstract »|Full Text »|PDF »
Overexpression of Vascular Endothelial Growth Factor 165 Drives Peritumor Interstitial Convection and Induces Lymphatic Drain: Magnetic Resonance Imaging, Confocal Microscopy, and Histological Tracking of Triple-labeled Albumin.
H. Dafni, T. Israely, Z. M. Bhujwalla, L. E. Benjamin, and M. Neeman (2002)
Cancer Res.
62, 6731-6739
|Abstract »|Full Text »|PDF »
Quality of Surgery Determinant for the Outcome of Patient With Gastric Cancer.
A. M. Kappas and D. H. Roukos (2002)
Ann. Surg. Oncol.
9, 828-830
|Full Text »|PDF »
The Formation of Lymphatic Vessels and Its Importance in the Setting of Malignancy.
M. Detmar and S. Hirakawa (2002)
J. Exp. Med.
196, 713-718
|Full Text »|PDF »
