| RRC ID |
27900
|
| Author |
Kobayashi N, Miyoshi S, Mikami T, Koyama H, Kitazawa M, Takeoka M, Sano K, Amano J, Isogai Z, Niida S, Oguri K, Okayama M, McDonald JA, Kimata K, Taniguchi S, Itano N.
|
| Title |
Hyaluronan deficiency in tumor stroma impairs macrophage trafficking and tumor neovascularization.
|
| Journal |
Cancer Res
|
| Abstract |
Despite the importance of stromal cells in tumor progression, our overall understanding of the molecular signals that regulate the complex cellular interactions within tumor stroma is limited. Here, we provide multiple lines of evidence that tumor-associated macrophages (TAM) preferentially traffic to stromal areas formed within tumors in a manner dependent on a hyaluronan (HA)-rich tumor microenvironment. To address the role of stroma-derived HA in macrophage recruitment, we disrupted the HA synthase 2 (Has2) gene in stromal fibroblasts using conditional gene targeting. The Has2 null fibroblasts showed severe impairment in recruiting macrophages when inoculated with tumor cells into nude mice, which shows the contribution of stroma-derived HA in intratumoral macrophage mobilization. Furthermore, a deficiency in stromal HA attenuated tumor angiogenesis and lymphangiogenesis concomitantly with impaired macrophage recruitment. Taken together, our results suggest that stromal HA serves as a microenvironmental signal for the recruitment of TAMs, which are key regulatory cells involved in tumor neovascularization.
|
| Volume |
70(18)
|
| Pages |
7073-83
|
| Published |
2010-9-15
|
| DOI |
10.1158/0008-5472.CAN-09-4687
|
| PII |
0008-5472.CAN-09-4687
|
| PMID |
20823158
|
| MeSH |
Animals
Female
Glucuronosyltransferase / genetics
Hyaluronan Synthases
Hyaluronic Acid / deficiency*
Lymphangiogenesis
Macrophages, Peritoneal / immunology
Macrophages, Peritoneal / pathology*
Mammary Neoplasms, Experimental / blood supply
Mammary Neoplasms, Experimental / immunology
Mammary Neoplasms, Experimental / metabolism*
Mammary Neoplasms, Experimental / pathology*
Mice
Mice, Inbred BALB C
Mice, Knockout
Mice, Transgenic
Neovascularization, Pathologic / metabolism
Neovascularization, Pathologic / pathology
Stromal Cells / pathology
|
| IF |
9.727
|
| Times Cited |
107
|
|
WOS Category
|
ONCOLOGY
|
| Resource |
| Mice |
RBRC01828
RBRC01834
RBRC02096 |
