Vascular Endothelial Growth Factor Receptors VEGFR-2 and VEGFR-3 are localised primarily to vasculature in human primary solid cancers

Smith, N.R., Baker, D., James, N.H., Ratcliffe, K., Jenkins, M., Ashton, S.E., Sproat, G., Swann, R., Gray, N., Ryan, A., Jürgensmeier, J.M. and Womack, C. 2010. Vascular Endothelial Growth Factor Receptors VEGFR-2 and VEGFR-3 are localised primarily to vasculature in human primary solid cancers. Clinical Cancer Research. 16 (14), pp. 3548-3561.

TitleVascular Endothelial Growth Factor Receptors VEGFR-2 and VEGFR-3 are localised primarily to vasculature in human primary solid cancers
AuthorsSmith, N.R., Baker, D., James, N.H., Ratcliffe, K., Jenkins, M., Ashton, S.E., Sproat, G., Swann, R., Gray, N., Ryan, A., Jürgensmeier, J.M. and Womack, C.
Abstract

Purpose: Vascular endothelial growth factor (VEGF) signaling is key to tumor angiogenesis and is an important target in the development of anticancer drugs. However, VEGF receptor (VEGFR) expression in human cancers, particularly the relative expression of VEGFR-2 and VEGFR-3 in tumor vasculature versus tumor cells, is poorly defined.

Experimental Design: VEGFR-2– and VEGFR-3–specific antibodies were identified and used in the immunohistochemical analysis of human primary cancers and normal tissue. The relative vascular localization of both receptors in colorectal and breast cancers was determined by coimmunofluorescence with vascular markers.

Results: VEGFR-2 and VEGFR-3 were expressed on vascular endothelium but not on malignant cells in 13 common human solid tumor types (n > 400, bladder, breast, colorectal, head and neck, liver, lung, skin, ovarian, pancreatic, prostate, renal, stomach, and thyroid). The signal intensity of both receptors was significantly greater in vessels associated with malignant colorectal, lung, and breast than adjacent nontumor tissue. In colorectal cancers, VEGFR-2 was expressed on both intratumoral blood and lymphatic vessels, whereas VEGFR-3 was found predominantly on lymphatic vessels. In breast cancers, both receptors were localized to and upregulated on blood vessels.

Conclusions: VEGFR-2 and VEGFR-3 are primarily localized to, and significantly upregulated on, tumor vasculature (blood and/or lymphatic) supporting the majority of solid cancers. The primary clinical mechanism of action of VEGF signaling inhibitors is likely to be through the targeting of tumor vessels rather than tumor cells. The upregulation of VEGFR-3 on tumor blood vessels indicates a potential additional antiangiogenic effect for dual VEGFR-2/VEGFR-3–targeted therapy.

JournalClinical Cancer Research
Journal citation16 (14), pp. 3548-3561
ISSN1078-0432
YearJul 2010
PublisherAmerican Association for Cancer Research
Digital Object Identifier (DOI)doi:10.1158/1078-0432
Publication dates
PublishedJul 2010

Related outputs

Cadherin-5: a biomarker for metastatic breast cancer with optimum efficacy in oestrogen receptor-positive breast cancers with vascular invasion
Fry, S., Robertson, C.E., Swann, R. and Dwek, M. 2016. Cadherin-5: a biomarker for metastatic breast cancer with optimum efficacy in oestrogen receptor-positive breast cancers with vascular invasion. British Journal of Cancer. 114, pp. 1019-1026.

Prediction of breast cancer risk based on profiling with common genetic variants
Mavaddat, N., Pharoah, P.D.P., Michailidou, K., Tyrer, J., Brook, M.N., Bolla, M.K., Wang, Q., Dennis, J., Dunning, A.M., Shah, M., Luben, R., Brown, J.C.C., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Czene, K., Darabi, H., Eriksson, M., Peto, J., Dos-Santos-Silva, I., Dudbridge, F., Johnson, N., Schmidt, M.K., Broeks, A., Verhoef, S., Rutgers, E.J., Swerdlow, A.J., Ashworth, A., Orr, N., Schoemaker, M.J., Figueroa, J.D., Chanock, S.J., Brinton, L., Lissowska, J., Couch, F.J., Olson, J.E., Vachon, C., Pankratz, V.S., Lambrechts, D., Wildiers, H., Van Ongeval, C., van Limbergen, E., Kristensen, V., Grenaker Alnaes, G., Nord, S., Borresen-Dale, A.-L., Nevanlinna, H., Muranen, T.A., Aittomaki, K., Blomqvist, C., Chang-Claude, J., Rudolph, A., Seibold, P., Flesch-Janys, D., Fasching, P.A., Haeberle, L., Ekici, A.B., Beckmann, M.W., Burwinkel, B., Marme, F., Schneeweiss, A., Sohn, C., Trentham-Dietz, A., Newcomb, P., Titus, L., Egan, K.M., Hunter, D.J., Lindstrom, S., Tamimi, R.M., Kraft, P., Rahman, N., Turnbull, C., Renwick, A., Seal, S., Li, J., Liu, J., Humphreys, K., Benitez, J., Pilar Zamora, M., Arias Perez, J.I., Menéndez, P., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Bogdanova, N.V., Antonenkova, N.N., Dörk, T., Anton-Culver, H., Neuhausen, S.L., Ziogas, A., Bernstein, L., Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C., van Asperen, C.J., Cox, A., Cross, S.S., Reed, M.W., Khusnutdinova, E., Bermisheva, M., Prokofyeva, D., Takhirova, Z., Meindl, A., Schmutzler, R.K., Sutter, C., Yang, R., Schürmann, P., Bremer, M., Christiansen, H., Park-Simon, T.-W., Hillemanns, P., Guenel, P., Truong, T., Menegaux, F., Sanchez, M., Radice, P., Peterlongo, P., Manoukian, S., Pensotti, V., Hopper, J.L., Tsimiklis, H., Apicella, C., Southey, M.C., Brauch, H., Brüning, T., Ko, Y.-D., Sigurdson, A.J., Doody, M.M., Hamann, U., Torres, D., Ulmer, H.U., Försti, A., Sawyer, E., Tomlinson, I., Kerin, M.J., Miller, N., Andrulis, I.L., Knight, J.A., Glendon, G., Marie Mulligan, A., Chenevix-Trench, G., Balleine, R., Giles, G.G., Milne, R.L., McLean, C.A., Lindblom, A., Margolin, S., Haiman, C.A., Henderson, B.E., Schumacher, F., Le Marchand, L., Eilber, U., Wang-Gohrke, S., Hooning, M.J., Hollestelle, A., van den Ouweland, A.M.W., Koppert, L.B., Carpenter, J., Clarke, C., Scott, R., Mannermaa, A., Kataja, V., Kosma, V.-M., Hartikainen, J.M., Brenner, H., Arndt, V., Stegmaier, C., Karina Dieffenbach, A., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Offit, K., Vijai, J., Robson, M., Rau-Murthy, R., Dwek, M., Swann, R., Annie Perkins, K., Goldberg, M.S., Labrèche, F., Dumont, M., Eccles, D.M., Tapper, W.J., Rafiq, S., John, E.M., Whittemore, A.S., Slager, S., Yannoukakos, D., Toland, A.E., Yao, S., Zheng, W., Halverson, S.L., Gonzalez-Neira, A., Pita, G., Rosario Alonso, M., Álvarez, N., Herrero, D., Tessier, D.C., Vincent, D., Bacot, F., Luccarini, C., Baynes, C., Ahmed, S., Maranian, M., Healey, C.S., Simard, J., Hall, P., Easton, D.F., Garcia-Closas, M., Dos Santos Silva, I., Channock, S.J., Zamora, M.P., Ignacio Arias Perez, J., Neuhasen, S.L., Prokofieva, D., Mulligan, A.M., Halman, C.A., Dieffenbach, A.K., Perkins, K.A. and Alonso, M.R. 2015. Prediction of breast cancer risk based on profiling with common genetic variants. J Natl Cancer Inst.. 107 (5).

Antibody validation of immunohistochemistry for biomarker discovery: Recommendations of a consortium of academic and pharmaceutical based histopathology researchers
Howat, W.J., Lewis, A., Jones, P., Kampf, C., Pontén, F., F, van der Loos, C.M., Gray, N., Womack, C. and Warford, A. 2014. Antibody validation of immunohistochemistry for biomarker discovery: Recommendations of a consortium of academic and pharmaceutical based histopathology researchers. Methods. 70 (1), pp. 34-38.

The DietCompLyf study: a prospective cohort study of breast cancer survival and phytoestrogen consumption
Swann, R., Perkins, K.A., Velentzis, L.S., Ciria, C., Dutton, S., Mulligan, A.A., Woodside, J., Cantwell, M.M., Leathem, A., Robertson, C.E. and Dwek, M. 2013. The DietCompLyf study: a prospective cohort study of breast cancer survival and phytoestrogen consumption. Maturitas. 75 (3), pp. 232-240.

The DietCompLyf study: a prospective longitudinal study of breast cancer survival
Swann, R., Perkins, A., Velentzis, L.S., Mulligan, A.M., Woodside, J., Cantwell, M.M., Dutton, S., Leathem, A., Robertson, C.E. and Dwek, M. 2012. The DietCompLyf study: a prospective longitudinal study of breast cancer survival. European Journal of Cancer. 48 (5), p. S216.

DietCompLyf study: a multi-centre UK study on breast cancer. What are the dietary and lifestyle changes following diagnosis?
Perkins, A., Swann, R., Woodside, J., Robertson, C.E., Dutton, S., Mulligan, A.M., Velentzis, L.S., Keshtgar, M.R., Leathem, A. and Dwek, M. 2012. DietCompLyf study: a multi-centre UK study on breast cancer. What are the dietary and lifestyle changes following diagnosis? European Journal of Cancer. 48 (5), p. S282.

19p13.1 is a triple negative-specific breast cancer susceptibility locus
Stevens, K.N., Fredericksen, Z., Vachon, C., Wang, X., Margolin, S., Lindblom, A., Nevanlinna, H., Greco, D., Aittomaki, K., Blomqvist, C., Chang-Claude, J., Vrieling, A., Flesch-Janys, D., Sinn, H.P., Wang-Gohrke, S., Nickels, S., Brauch, H., Ko, Y.-D., Fischer, H.P., Schmutzler, R.K., Meindl, A., Bartram, C.R., Schott, S., Engel, C., Godwin, A.K., Weaver, J., Pathak, H.B., Sharma, P., Brenner, H., Muller, H., Arndt, V., Stegmaier, C., Miron, P., Yannoukakos, D., Stavropoulou, A., Fountzilas, G., Gogas, H.J., Swann, R., Dwek, M., Perkins, A., Milne, R.L., Benitez, J., Zamora, M.P., Ignacio Arias Perez, J., Bojesen, S.E., Nielsen, S.F., Nordestgaard, B.G., Flyger, H., Guenel, P., Truong, T., Menegaux, F., Cordina-Duverger, E., Burwinkel, B., Marme, F., Schneeweiss, A., Sohn, C., Sawyer, E., Tomlinson, I., Kerin, M.J., Peto, J., Johnson, N., Fletcher, O., Dos Santos Silva, I., Fasching, P.A., Beckmann, M.W., Hartmann, A., Ekici, A.B., Lophatananon, A., Muir, K., Puttawibul, P., Wiangnon, S., Schmidt, M.K., Broeks, A., Braaf, L.M., Rosenberg, E.H., Hopper, J.L., Apicella, C., Park, D.J., Southey, M.C., Swerdlow, A.J., Ashworth, A., Orr, N., Schoemaker, M.J., Anton-Culver, H., Ziogas, A., Bernstein, L., Clarke Dur, C., Shen, C.Y., Yu, J.C., Hsu, H.M., Hsiung, C.N., Hamann, U., Dünnebier, T., Rüdiger, T., Ulmer, H.U., Pharoah, P.D.P., Dunning, A.M., Humphreys, M.K., Wang, Q., Cox, A., Cross, S.S., Reed, M.W.R., Hall, P., Czene, K., Ambrosone, C.B., Ademuyiwa, F., Hwang, H., Eccles, D.M., Garcia-Closas, M., Figueroa, J.D., Sherman, M.E., Lissowska, J., Devilee, P., Seynaeve, C., Tollenaar, R.A.E.M., Hooning, M.J., Andrulis, I.L., Knight, J.A., Glendon, G., Mulligan, A.M., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., John, E.M., Miron, A., Grenaker Alnaes, G., Kristensen, V., Borresen-Dale, A.L., Giles, G.G., Baglietto, L., McLean, C.A., Severi, G., Kose, M.L., Pankratz, V.S., Slager, S., Olson, J.E., Radice, P., Peterlongo, P., Manoukian, S., Barile, M., Lambrechts, D., Hatse, S., Dieudonne, A.S., Christiaens, M.R., Chenevix-Trench, G., Beesley, J., Chen, X., Mannermaa, A., Kosma, V.-M., Hartikainen, J.M., Soini, Y., Easton, D.F., Couch, F.J. and Borrensen-Dale, A.-L. 2012. 19p13.1 is a triple negative-specific breast cancer susceptibility locus. Cancer Research. 72 (7), pp. 1795-1803.

Genome-wide association analysis identifies three new breast cancer susceptibility loci
Ghoussaini, M., Fletcher, O., Michailidou, K., Turnbull, C., Schmidt, M.K., Dicks, E., Dennis, J., Wang, Q., Humphreys, M.K., Luccarini, C., Baynes, C., Conroy, D., Maranian, M., Ahmed, S., Driver, K., Johnson, N., Orr, N., Dos Santos Silva, I., Waisfisz, Q., Meijers-Heijboer, H., Uitterlinden, A.G., Rivadeneira, F., Hall, P., Czene, K., Irwanto, A., Liu, J., Nevanlinna, H., Aittomaki, K., Blomqvist, C., Meindl, A., Schmutzler, R.K., Muller-Myhsok, B., Lichtner, P., Chang-Claude, J., Hein, R., Nickels, S., Flesch-Janys, D., Tsimiklis, H., Makalic, E., Schmidt, D., Bui, M., Hopper, J.L., Apicella, C., Park, D.J., Southey, M.C., Hunter, D.J., Channock, S.J., Broeks, A., Verhoef, S., Hogervorst, F.B.L., Fasching, P.A., Lux, M.P., Beckmann, M.W., Ekici, A.B., Sawyer, E., Tomlinson, I., Kerin, M.J., Marme, F., Schneeweiss, A., Sohn, C., Burwinkel, B., Guenel, P., Truong, T., Cordina-Duverger, E., Menegaux, F., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Milne, R.L., Alonso, M.R., Gonzalez-Neira, A., Benitez, J., Anton-Culver, H., Ziogas, A., Bernstein, L., Clarke Dur, C., Brenner, H., Muller, H., Arndt, V., Stegmaier, C., Justenhoven, C., Brauch, H., Brüning, T., Wang-Gohrke, S., Eilber, U., Dörk, T., Schürmann, P., Bremer, M., Hillemanns, P., Bogdanova, N.V., Antonenkova, N.N., Rogov, Y.I., Karstens, J.H., Bermisheva, M., Prokofieva, D., Khusnutdinova, E., Lindblom, A., Margolin, S., Mannermaa, A., Kataja, V., Kosma, V.-M., Hartikainen, J.M., Lambrechts, D., Yesilyurt, B.T., Floris, G., Leunen, K., Manoukian, S., Bonanni, B., Fortuzzi, S., Peterlongo, P., Couch, F.J., Wang, X., Stevens, K.N., Lee, A., Giles, G.G., Baglietto, L., Severi, G., McLean, C.A., Grenaker Alnaes, G., Kristensen, V., Borrensen-Dale, A.-L., John, E.M., Miron, A., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Kauppila, S., Andrulis, I.L., Glendon, G., Mulligan, A.M., Devilee, P., van Asperen, C.J., Tollenaar, R.A.E.M., Seynaeve, C., Figueroa, J.D., Garcia-Closas, M., Brinton, L., Lissowska, J., Hooning, M.J., Hollestelle, A., Oldenburg, R.A., van den Ouweland, A.M.W., Cox, A., Reed, M.W.R., Shah, M., Jakubowska, A., Lubinski, J., Jaworska, K., Durda, K., Jones, M., Schoemaker, M.J., Ashworth, A., Swerdlow, A.J., Beesley, J., Chen, X., Muir, K., Lophatananon, A., Rattanamongkongul, S., Chaiwerawattana, A., Kang, D., Yoo, K.Y., Noh, D.Y., Shen, C.Y., Yu, J.C., Wu, P.E., Hsiung, C.N., Perkins, A., Swann, R., Velentzis, L.S., Eccles, D.M., Tapper, W.J., Gerty, S.M., Graham, N.J., Ponder, B.A.J., Chenevix-Trench, G., Pharoah, P.D.P., Lathrop, M., Dunning, A.M., Rahman, N., Peto, J. and Easton, D.F. 2012. Genome-wide association analysis identifies three new breast cancer susceptibility loci. Nature Genetics. 44 (3), pp. 312-318.

Abstract B76 - An overview of the DietCompLyf study - a multicentre UK study to evaluate the role of diet, lifestyle and complementary medicine use on breast cancer recurrence
Swann, R., Perkins, A., Dahya, P., Woodside, J., Dutton, S., Robertson, C.E., Velentzis, L.S., Leathem, A. and Dwek, M. 2011. Abstract B76 - An overview of the DietCompLyf study - a multicentre UK study to evaluate the role of diet, lifestyle and complementary medicine use on breast cancer recurrence. National Cancer Research Institute (NCRI) Cancer Conference 2011. BT Convention Centre, Liverpool, UK 06 - 09 Nov 2011

Permalink - https://westminsterresearch.westminster.ac.uk/item/90264/vascular-endothelial-growth-factor-receptors-vegfr-2-and-vegfr-3-are-localised-primarily-to-vasculature-in-human-primary-solid-cancers


Share this
Tweet
Email