当前位置： SCI文献检索 > CANCER RESEARCH期刊下所有文献 > Tumor-secreted vascular endothelial growth factor-C is necessary for prostate cancer lymphangiogenesis, but lymphangiogenesis is unnecessary for lymph node metastasis.

Tumor-secreted vascular endothelial growth factor-C is necessary for prostate cancer lymphangiogenesis, but lymphangiogenesis is unnecessary for lymph node metastasis.

Abstract：

:Dissemination to draining lymph nodes is a frequent first step in prostate cancer metastasis. Although tumors metastasize to lymph nodes via the lymphatics, the importance of lymphangiogenesis in mediating the process remains controversial. Here, we inhibit intratumoral lymphangiogenesis in s.c. and surgical orthotopic implantation mouse models of human prostate cancer using several strategies. Stable expression of small interfering RNAs (siRNA) targeted against human vascular endothelial growth factor-C (VEGF-C) in PC-3 cells reduced intratumoral lymphatics by 99% in s.c. tumors, indicating that tumor-secreted VEGF-C is necessary for lymphangiogenesis. Expression of siRNAs against human VEGF-A somewhat reduced tumor lymphangiogenesis. Secretion of a soluble VEGF receptor-3/Flt4 fusion protein by PC-3 cells reduced intratumoral lymphatics by 100% in s.c. tumors. Combination of soluble Flt4 and VEGF-C siRNA yielded >92% reduction of intratumoral lymphatics in orthotopic prostate tumors. However, metastasis to lymph nodes was not significantly affected regardless of intratumoral lymphatic vessel density. The abundance of marginal lymphatics at the tumor-stromal interface was unchanged in orthotopic tumors whose intratumoral lymphatics were inhibited, suggesting that these marginal vessels could be sufficient for lymph node metastasis. Hematogenous metastasis (blood tumor burden, lung metastasis) correlated with degree of lymph node invasion. We also analyzed the lymphatics in spontaneous transgenic adenocarcinomas of the mouse prostate which metastasize to lymph nodes. Progression from well-differentiated prostate intraepithelial neoplasia to metastatic, undifferentiated adenocarcinoma was accompanied by loss of lymphatics. These results suggest that tumor-secreted VEGF-C and, to a lesser extent, VEGF-A, are important for inducing prostate cancer intratumoral lymphangiogenesis but are unnecessary for lymph node metastasis.

journal_name

Cancer Res

journal_title

Cancer research

authors

Wong SY,Haack H,Crowley D,Barry M,Bronson RT,Hynes RO

doi

10.1158/0008-5472.CAN-05-0901

subject

Has Abstract

pub_date

2005-11-01 00:00:00

pages

9789-98

issue

eissn

0008-5472

issn

1538-7445

pii

65/21/9789

journal_volume

pub_type

杂志文章

在线工具

Tumor-secreted vascular endothelial growth factor-C is necessary for prostate cancer lymphangiogenesis, but lymphangiogenesis is unnecessary for lymph node metastasis.