Pericytes from human non-small cell lung carcinomas: an attractive target for anti-angiogenic therapy.
Anti-angiogenic strategies have largely focused on endothelial cells and progenitors. However, pericytes are also an important component of vasculature. Perivascular cells from normal tissues have been widely reported, yet have not been extensively studied from human tumors. We have investigated pericytes from tumors of patients with lung cancer, the leader of cancer-related deaths in both men and women. Antibodies and magnetic beads were used to isolate cells from non-small cell lung carcinomas (NSCLC). The morphology of the pericytes was distinct with multiple elongated cytoplasmic extensions. Molecular expression of angiogenic genes was quantified by RT-PCR. Flow cytometric analysis shows that NSCLC pericytes express antigens such NG2 and VEGFR1 and present the ganglioside 3G5. The value of pericytes as models of tumor vasculature was demonstrated in cell-culture-based angiogenesis assays such as tube formation and proliferation. Results show that pericytes from some NSCLC but not all were able to maintain tubes networks on Matrigel. Pericyte function can be influenced by angiogenic growth factors or anti-angiogenic agents. Pericytes displayed invasive action against NSCLC clusters in the absence of other cell types. Perivascular cells contribute to the progression of disease and are an attractive target for anti-angiogenic therapy.
Bagley
Rebecca G
RG
Genzyme Corporation, Framingham, MA 01701-9322, USA. Rebecca.Bagley@Genzyme.com
Rouleau
Cecile
C
Morgenbesser
Sharon D
SD
Weber
William
W
Cook
Brian P
BP
Shankara
Srinivas
S
Madden
Stephen L
SL
Teicher
Beverly A
BA
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000941:Antigens / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002465:Cell Movement; D005260:Female; D015870:Gene Expression; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D018189:Immunomagnetic Separation; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D009389:Neovascularization, Pathologic / Q000235:genetics; D020286:Pericytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D011509:Proteoglycans / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
D020533:Angiogenesis Inhibitors; D000941:Antigens; D006133:Growth Substances; D011509:Proteoglycans; D040281:Vascular Endothelial Growth Factor Receptor-1; D000099216:Chondroitin Sulfate Proteoglycan 4