Abstract
Caveolin, a major structural component of specialized plasma membrane invaginations (caveolae) that participate in diverse cellular activities, has been implicated in the pathogenesis of several human diseases, including cancer. We showed in earlier studies that caveolin-1 (cav-1) is consistently and strongly overexpressed in metastatic prostate cancer and is secreted in a biologically active form by virulent prostate cancer cells. Using both in vitro and in vivo model systems, we now present evidence supporting a proangiogenic role for cav-1 in prostate cancer development and progression. Recombinant cav-1 (rcav-1) was taken up by cav-1-/- endothelial cells through either a lipid raft/caveolae- or clathrin-dependent mechanism, leading to specific angiogenic activities (tubule formation, cell migration, and nitric oxide production) that were mediated by rcav-1 stimulation of the PI3K-Akt-eNOS signaling module. Pathologic angiogenesis induced by cav-1 in prostate cancer-bearing mice correlated with an increased frequency, number, and size of lung metastases. We propose that in addition to its antiapoptotic role, cav-1 secreted by prostate cancer cells functions critically as a proangiogenic factor in metastatic progression of this tumor. These new insights into cav-1 function in prostate cancer may provide a base for the design of clinically applicable therapeutic strategies.
| Original language | English |
|---|---|
| Pages (from-to) | 731-739 |
| Number of pages | 9 |
| Journal | Cancer Research |
| Volume | 68 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Feb 1 2008 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Tumor cell-secreted caveolin-1 has proangiogenic activities in prostate cancer. / Tahir, Salahaldin A.; Yang, Guang; Goltsov, Alexei A.; Watanabe, Masami; Tabata, Ken Ichi; Addai, Josephine; Fattah, El Moataz Abdel; Kadmon, Dov; Thompson, Timothy C.
In: Cancer Research, Vol. 68, No. 3, 01.02.2008, p. 731-739.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Tumor cell-secreted caveolin-1 has proangiogenic activities in prostate cancer
AU - Tahir, Salahaldin A.
AU - Yang, Guang
AU - Goltsov, Alexei A.
AU - Watanabe, Masami
AU - Tabata, Ken Ichi
AU - Addai, Josephine
AU - Fattah, El Moataz Abdel
AU - Kadmon, Dov
AU - Thompson, Timothy C.
PY - 2008/2/1
Y1 - 2008/2/1
N2 - Caveolin, a major structural component of specialized plasma membrane invaginations (caveolae) that participate in diverse cellular activities, has been implicated in the pathogenesis of several human diseases, including cancer. We showed in earlier studies that caveolin-1 (cav-1) is consistently and strongly overexpressed in metastatic prostate cancer and is secreted in a biologically active form by virulent prostate cancer cells. Using both in vitro and in vivo model systems, we now present evidence supporting a proangiogenic role for cav-1 in prostate cancer development and progression. Recombinant cav-1 (rcav-1) was taken up by cav-1-/- endothelial cells through either a lipid raft/caveolae- or clathrin-dependent mechanism, leading to specific angiogenic activities (tubule formation, cell migration, and nitric oxide production) that were mediated by rcav-1 stimulation of the PI3K-Akt-eNOS signaling module. Pathologic angiogenesis induced by cav-1 in prostate cancer-bearing mice correlated with an increased frequency, number, and size of lung metastases. We propose that in addition to its antiapoptotic role, cav-1 secreted by prostate cancer cells functions critically as a proangiogenic factor in metastatic progression of this tumor. These new insights into cav-1 function in prostate cancer may provide a base for the design of clinically applicable therapeutic strategies.
AB - Caveolin, a major structural component of specialized plasma membrane invaginations (caveolae) that participate in diverse cellular activities, has been implicated in the pathogenesis of several human diseases, including cancer. We showed in earlier studies that caveolin-1 (cav-1) is consistently and strongly overexpressed in metastatic prostate cancer and is secreted in a biologically active form by virulent prostate cancer cells. Using both in vitro and in vivo model systems, we now present evidence supporting a proangiogenic role for cav-1 in prostate cancer development and progression. Recombinant cav-1 (rcav-1) was taken up by cav-1-/- endothelial cells through either a lipid raft/caveolae- or clathrin-dependent mechanism, leading to specific angiogenic activities (tubule formation, cell migration, and nitric oxide production) that were mediated by rcav-1 stimulation of the PI3K-Akt-eNOS signaling module. Pathologic angiogenesis induced by cav-1 in prostate cancer-bearing mice correlated with an increased frequency, number, and size of lung metastases. We propose that in addition to its antiapoptotic role, cav-1 secreted by prostate cancer cells functions critically as a proangiogenic factor in metastatic progression of this tumor. These new insights into cav-1 function in prostate cancer may provide a base for the design of clinically applicable therapeutic strategies.
UR - http://www.scopus.com/inward/record.url?scp=38849095886&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38849095886&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-07-2668
DO - 10.1158/0008-5472.CAN-07-2668
M3 - Article
C2 - 18245473
AN - SCOPUS:38849095886
VL - 68
SP - 731
EP - 739
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 3
ER -