Open Access Research

Tumor growth and angiogenesis is impaired in CIB1 knockout mice

Mohamed A Zayed14, Weiping Yuan25, Dan Chalothorn3, James E Faber3 and Leslie V Parise12*

Author Affiliations

1 Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

2 Department of Biochemistry & Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

3 Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

4 Current Address: Department of Surgery, Division of Vascular Surgery, Stanford University Hospital & Clinics, Stanford, CA, USA

5 Current Address: Institute of Hematology, Chinese Academy of Medical Sciences, Tianjin, China

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Journal of Angiogenesis Research 2010, 2:17  doi:10.1186/2040-2384-2-17

Published: 30 August 2010

Abstract

Background

Pathological angiogenesis contributes to various ocular, malignant, and inflammatory disorders, emphasizing the need to understand this process more precisely on a molecular level. Previously we found that CIB1, a 22 kDa regulatory protein, plays a critical role in endothelial cell function, angiogenic growth factor-mediated cellular functions, PAK1 activation, MMP-2 expression, and in vivo ischemia-induced angiogenesis. Since pathological angiogenesis is highly dependent on many of these same processes, we hypothesized that CIB1 may also regulate tumor-induced angiogenesis.

Methods

To test this hypothesis, we allografted either murine B16 melanoma or Lewis lung carcinoma cells into WT and CIB1-KO mice, and monitored tumor growth, morphology, histology, and intra-tumoral microvessel density.

Results

Allografted melanoma tumors that developed in CIB1-KO mice were smaller in volume, had a distinct necrotic appearance, and had significantly less intra-tumoral microvessel density. Similarly, allografted Lewis lung carcinoma tumors in CIB1-KO mice were smaller in volume and mass, and appeared to have decreased perfusion. Intra-tumoral hemorrhage, necrosis, and perivascular fibrosis were also increased in tumors that developed in CIB1-KO mice.

Conclusions

These findings suggest that, in addition to its other functions, CIB1 plays a critical role in facilitating tumor growth and tumor-induced angiogenesis.