Abstract
Tumor-induced blood vessel formation is a key process for the growth and spread of solid tumors, traditionally attributed to activated host endothelial cells (angiogenesis). Recently, highly aggressive cancer cells have been shown to form vascular channels in the absence of endothelial cells (vasculogenic mimicry). In this work, we have focused on the common dependence of both processes in their interactions with the surrounding extracellular matrix. We had previously described a human recombinant anti-laminin antibody that blocked the capillary morphogenesis of human endothelial cells. Here, we demonstrate that the purified antibody is capable of inhibiting channel formation by human cancer cells, suggesting a common morphogenic pathway in both processes. Moreover, matrix-embedded cells producing antibody fragments may render the surrounding matrix non-permissive for aggressive tumor cells. These results open the way for the development of new therapeutic strategies for cancer.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ades EW, Candal FJ, Swerlick RA, George VG, Summers S, Bosse DC, Lawley TJ (1992) HMEC-1: establishment of an immortalized human microvascular endothelial cell line. J Invest Dermatol 99:683
Alitalo K, Carmeliet P (2002) Molecular mechanisms of lymphangiogenesis in health and disease. Cancer Cell 1:219
Álvarez-Vallina L (2001) Genetic approaches for antigen-selective cell therapy. Curr Gene Ther 1:385
Bischoff J (1997) Cell adhesion and angiogenesis. J Clin Invest 100:S37
Bissell MJ, Radisky D (2001) Putting tumours in context. Nat Rev Cancer 1:46
Bittner M, Meltzer P, Chen Y, Jiang Y, Seftor E, Hendrix M, Radmacher M, Simon R, Yakhini Z, Ben-Dor A, Sampas N, Dougherty E, Wang E, Marincola F, Gooden C, Lueders J, Glatfelter A, Pollock P, Carpten J, Gillanders E, Leja D, Dietrich K, Beaudry C, Berens M, Alberts D, Sondak V (2000) Molecular classification of cutaneous malignant melanoma by gene expression profiling. Nature 406:536
Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407:249
Chang YS, di Tomaso E, McDonald DM, Jones R, Jain RK, Munn LL (2000) Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood. Proc Natl Acad Sci USA 97:14608
Chester J, Ruchatz A, Gough M, Crittenden M, Chong H, Loic-Cosset F, Diaz RM, Harrington K, Álvarez-Vallina L, Vile R (2002) Tumor antigen-specific induction of transcriptionally targeted retroviral vectors from chimeric immune receptor-modified T cells. Nat Biotechnol 20:256
Colognato H, Yurchenco P (2000) Form and function: the laminin family of heterotrimers. Dev Dyn 218:213
Folberg R, Hendrix MJ, Maniotis AJ (2000) Vasculogenic mimicry and tumor angiogenesis. Am J Pathol 156:361
Folkman J (1972) Anti-angiogenesis: new concept for therapy of solid tumors. Ann Surg 175:40930.
Hawkins RE, Russell SJ, Winter G (1992) Selection of phage antibodies by binding affinity: mimicking affinity maturation. J Mol Biol 226:889
Hendrix MJ, Seftor EA, Meltzer PS, Gardner LM, Hess AR, Kirschmann DA, Schatteman GC, Seftor RE (2001) Expression and functional significance of VE-cadherin in aggressive human melanoma cells: role in vasculogenic mimicry. Proc Natl Acad Sci USA 98:8018
Hendrix MJ, Seftor RE, Seftor EA, Gruman LM, Lee LM, Nickoloff BJ, Miele L, Sheriff DD, Schatteman GC (2002) Transendothelial function of human metastatic melanoma cells: role of the microenvironment in cell-fate determination. Cancer Res 62:665
Hoang MP, Selim MA, Bentley RC, Burchette JL, Shea CR (2001) CD34 expression in desmoplastic melanoma. J Cutan Pathol 28:508
Kobayashi H, Shirakawa K, Kawamoto S, Saga T, Sato N, Hiraga A, Watanabe I, Heike Y, Togashi K, Konishi J, Brechbiel MW, Wakasugi H (2002) Rapid accumulation and internalization of radiolabeled herceptin in an inflammatory breast cancer xenograft with vasculogenic mimicry predicted by the contrast-enhanced dynamic MRI with the macromolecular contrast agent G6-(1B4M-Gd)(256). Cancer Res 62:860
Maniotis AJ, Folberg R, Hess A, Seftor EA, Gardner LM, Pe'er J, Trent JM, Meltzer PS, Hendrix MJ (1999) Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol 155:739
McDonald DM, Foss AJ (2000) Endothelial cells of tumor vessels: abnormal but not absent. Cancer Metastasis Rev 19:109
McDonald DM, Munn L, Jain RK (2000) Vasculogenic mimicry: how convincing, how novel, and how significant? Am J Pathol 156:383
Meyer GT, Matthias LJ, Noack L, Vadas MA, Gamble JR (1997) Lumen formation during angiogenesis in vitro involves phagocytic activity, formation and secretion of vacuoles, cell death, and capillary tube remodelling by different populations of endothelial cells. Anat Rec 249:327
Rusolahti E (2002) Specialization of tumour vasculature. Nat Rev Cancer 2:8321
Sanz L, Kristensen P, Russell SJ, Ramírez García JR, Álvarez-Vallina L (2001) Generation and characterization of recombinant human antibodies specific for native laminin epitopes: potential application in cancer therapy. Cancer Immunol Immunother 50:557
Sanz L, Kristensen P, Blanco B, Facteau S, Russell SJ, Winter G, Álvarez-Vallina L (2002) Single-chain antibody-based gene therapy: inhibition of tumor growth by in situ production of phage-derived human antibody fragments blocking functionally active sites of cell-associated matrices. Gene Ther 9:1049
Sanz L, Pascual M, Muñoz A, González MA, Hernández Salvador C, Álvarez-Vallina L (2002) Development of a computer-assisted high-throughput screening platform for anti-angiogenic screening. Microvasc Res 63:335
Satyamoorthy K, DeJesus E, Linnenbach AJ, Kraj B, Kornreich DL, Rendle S, Elder DE, Herlyn M (1997) Melanoma cell lines from different stages of progression and their biological and molecular analyses. Melanoma Res 7 [Suppl 2]:S35
Seftor RE, Seftor EA, Koshikawa N, Meltzer PS, Gardner LM, Bilban M, Stetler-Stevenson WG, Quaranta V, Hendrix MJ (2001) Cooperative interactions of laminin 5 gamma2 chain, matrix metalloproteinase-2, and membrane type-1-matrix/metalloproteinase are required for mimicry of embryonic vasculogenesis by aggressive melanoma. Cancer Res 61:6322
Sharma N, Seftor RE, Seftor EA, Gruman LM, Heidger PM Jr, Cohen MB, Lubaroff DM, Hendrix MJ (2002) Prostatic tumor cell plasticity involves cooperative interactions of distinct phenotypic subpopulations: role in vasculogenic mimicry. Prostate 50:189
Sood AK, Seftor EA, Fletcher MS, Gardner LM, Heidger PM, Buller RE, Seftor RE, Hendrix MJ (2001) Molecular determinants of ovarian cancer plasticity. Am J Pathol 158:1279
Timpl R (1996) Macromolecular organization of basement membranes. Curr Opin Cell Biol 8:618
Watson SA, Durrant LG, Morris DL (1990) The effect of the E2 prostaglandin enprostil, and the somatostatin analogue SMS 201 995, on the growth of a human gastric cell line, MKN45G. Int J Cancer 45:90
Acknowledgements
Financial support for this research was provided to L. A-V. from the Fondo de Investigación Sanitaria (grant PI021144) and the Ministerio de Ciencia y Tecnología (grant BIO2001-0385). L. S. was supported by grants from the 5th framework of the European Community to L. A-V. B. B. was supported by a Comunidad Autónoma de Madrid training grant 01/0369/2000.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sanz, L., Feijóo, M., Blanco, B. et al. Generation of non-permissive basement membranes by anti-laminin antibody fragments produced by matrix-embedded gene-modified cells. Cancer Immunol Immunother 52, 643–647 (2003). https://doi.org/10.1007/s00262-003-0400-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00262-003-0400-0