Analysis of Mural Cell Recruitment to Tumor Vessels

Abstract

Background-Tumor blood vessels are both structurally and functionally abnormal compared with normal vessels. A limited support of mural cells may contribute to these abnormalities. Here, we characterized mural cell recruitment in 2 mouse tumor models and addressed the question of why tumor vessels fail to recruit a proper coat of mural cells. Methods and Results-We studied mural cell recruitment to the vasculature of 2 transplantable mouse tumor models, T241 fibrosarcoma and KRIB osteosarcoma. We found that both tumors formed a vessel network with heterogeneous and highly abnormal organization of mural cells.

Inhibition of Vascular Endothelial Growth Factor (VEGF) Signaling in Cancer Causes Loss of Endothelial Fenestrations, Regression of Tumor Vessels, and Appearance of Basement Membrane Ghosts

“…Blood vessels in mice deficient in PDGF-B or PDGFR-␤ do not recruit pericytes and have abnormalities reminiscent of those of tumor vessels. 10,48 Treatment with AG013736 or VEGF-Trap normalized the phenotype of some pericytes, as manifested by a tighter association with endothelial cells of surviving vessels. This change is consistent with previous reports of the normalization of tumor vessels by VEGF/VEGFR inhibition.…”

“…8,9 Even pericytes (mural cells) of tumor vessels are abnormal, as evidenced by altered gene expression and loss of intimate contact with endothelial cells. 10,11 Abnormalities of the basement membrane of tumor vessels are also present and reflect the disturbances of endothelial cells and pericytes. 12 We reasoned that a better understanding of these abnormalities and how they respond to treatment could give insight into the cellular effects of angiogenesis inhibitors.…”

PDGF-D is a potent transforming and angiogenic growth factor

“…The failure of tumour vessels to properly recruite perivascular cells (vascular smooth muscle cells and pericytes) to stabilize the vessels is thought to contribute to the abnormal phenotype of tumour vessels (Abramsson et al, 2002). As PDGFs are known to be potent mitogens for perivascular cells, and affect their migration, we studied the structure of the tumour vasculature by staining tumour sections for PECAM and SMA expression to reveal possible differences.…”

Platelet-Derived Growth Factor-B Normalizes Micromorphology and Vessel Function in Vascular Endothelial Growth Factor-A-Induced Squamous Cell Carcinomas

“…Yet it also plays a crucial role in the establishment of functional vessels in the tumor. 26,27 Tumor-inducing paracrine functions of PDGF-B have been demonstrated in our HaCaT skin carcinogenesis model. Transfection of the nontumorigenic keratinocyte cell line HaCaT with human (h)PDGF-B resulted in benign tumor growth that was mediated by initial stromal activation and subsequent stromal and vascular maturation.…”