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J Angiogenes Res. 2010 Aug 30;2:17. doi: 10.1186/2040-2384-2-17.

Tumor growth and angiogenesis is impaired in CIB1 knockout mice.

Author information

  • 1Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. parise@med.unc.edu.

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.

PMID:
20804551
[PubMed]
PMCID:
PMC2941741
Free PMC Article

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