Stimulation of angiogenesis as an explanation of Matrigel-enhanced tumorigenicity.
Matrigel, a reconstituted extract of basement membrane, enhances the growth of different human cancer cell lines when transplanted into nude mice. Here that stimulation was confirmed in the BALB/c murine mammary-tumor cell line M3MC, as well as in human colon (SW948) and mammary (MDA-MB-468) carcinoma cell lines transplanted in nude and SCID mice, respectively. Subcutaneous and intra-mammary fat-pad inoculations of Matrigel alone generated an angiogenic response which was macroscopically evident by day 9. Histological analysis of the local host reaction occurring at the site of injection revealed an early peripheral fibroblast response, followed by mononuclear cell infiltration, solid and hollow fibroblast cords projections from the edge to the center of the Matrigel plug, and finally capillary ingrowths. Conditioned media obtained from the gels generated in vivo, acted as very strong chemoattractants for mouse lung capillary endothelial cells, stimulating their motility between 38 and 82 times with respect to the control. Our results suggest an important role of host cells recruited by Matrigel, which could favor angiogenesis of the area and thus facilitate the growth of tumor cells co-inoculated with the basement membrane extract.
Bonfil
R D
RD
Fundación de Investigación del Cáncer, Buenos Aires, Argentina.
Vinyals
A
A
Bustuoabad
O D
OD
Llorens
A
A
Benavides
F J
FJ
Gonzalez-Garrigues
M
M
Fabra
A
A
D000230:Adenocarcinoma / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D003094:Collagen / Q000378:metabolism / Q000633:toxicity*; D017364:Collagenases / Q000378:metabolism; D003110:Colonic Neoplasms / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005260:Female; D006801:Humans; D007797:Laminin / Q000633:toxicity*; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D020780:Matrix Metalloproteinase 9; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D009389:Neovascularization, Pathologic; D011509:Proteoglycans / Q000633:toxicity*; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D017364:Collagenases; D020780:Matrix Metalloproteinase 9