| RRC ID |
10883
|
| 著者 |
Yamamura H, Hirano N, Koyama H, Nishizawa Y, Takahashi K.
|
| タイトル |
Loss of smooth muscle calponin results in impaired blood vessel maturation in the tumor-host microenvironment.
|
| ジャーナル |
Cancer Sci
|
| Abstract |
The interactions between malignant cells and the microenvironment of the local host tissue play a critical role in tumor growth, metastasis and their response to treatment modalities. We investigated the roles of smooth muscle calponin (Cnn1, also called calponin h1 or basic calponin) in the development of tumor vascul ature in vivo by analyzing mutant mice lacking the Cnn1 gene. Here we show that loss of Cnn1 in host mural cells prevents maturation of tumor vasculature. In vitro studies showed that platelet-derived growth factor B-induced vascular smooth muscle migration was downregulated by the Cnn1-deficiency, and forced expression of Cnn1 restored migration. Moreover, destruction of established tumor mass by treatment with an antivascular endothelial growth factor antibody was markedly enhanced in Cnn1-deficient mice. These data, coupled with the knowledge that structural fragility of normal blood vessels is caused by loss of the Cnn1 gene, suggest that Cnn1 plays an important role in the maturation of blood vessels, and may have implications for therapeutic strategies targeting tumor vasculature for treatment of human cancers.
|
| 巻・号 |
98(5)
|
| ページ |
757-63
|
| 公開日 |
2007-5-1
|
| DOI |
10.1111/j.1349-7006.2007.00452.x
|
| PII |
CAS452
|
| PMID |
17391313
|
| MeSH |
Actins / analysis
Animals
Antibodies / pharmacology
Antigens, CD34 / analysis
Apoptosis / drug effects
Becaplermin
Blood Vessels / drug effects
Blood Vessels / metabolism*
Blood Vessels / pathology
Calcium-Binding Proteins / genetics
Calcium-Binding Proteins / physiology*
Carcinoma, Lewis Lung / blood supply*
Carcinoma, Lewis Lung / genetics
Carcinoma, Lewis Lung / pathology
Cell Line, Tumor
Cell Movement / drug effects
Cells, Cultured
Immunohistochemistry
Male
Melanoma, Experimental / blood supply*
Melanoma, Experimental / genetics
Melanoma, Experimental / pathology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Mice, Nude
Microfilament Proteins / genetics
Microfilament Proteins / physiology*
Muscle, Smooth / chemistry
Platelet Endothelial Cell Adhesion Molecule-1 / analysis
Platelet-Derived Growth Factor / pharmacology
Proto-Oncogene Proteins c-sis
Vascular Endothelial Growth Factor A / immunology
|
| IF |
4.966
|
| 引用数 |
15
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
LLC(RCB0558) |
