Jiang, Wen Guo ![]() ![]() ![]() ![]() |
Abstract
Purpose: Hepatocyte growth factor/scatter factor (HGF/SF) is known to increase the invasiveness and migration of cancer cells in vitro and induce angiogenesis. This study examined if inhibition of HGF/SF receptor expression by cancer cells and HGF/SF expression by stromal fibroblasts affects the growth of mammary cancer. Experimental Design: Transgenes encoding ribozymes to specifically target human HGF/SF receptor (pLXSN-MET) or HGF/SF (pLXSN-HGF) were constructed using a pLXSN retroviral vector. Human mammary cancer cells MDA MB 231 was transduced with pLXSN-MET (MDA+/+). A human fibroblast cell line MRC5, which produces bioactive HGF/SF, was transduced with pLXSN-HGF (MRC5+/+). These cells were used in a nude mice breast tumor model. Results: HGF receptor in MDA+/+ cells and HGF in MRC5+/+cells were successfully removed with respective ribozymes as shown by reverse transcription-PCR and Western blotting, respectively. MDA+/+ was found to have reduced invasiveness when stimulated with HGF/SF. MRC5+/+ exhibited a significant reduction in HGF/SF production. When injected into athymic nude mice, MDA+/+ exhibited a slower rate of growth, compared with the wild type (MDA?/?), and the cells transduced with control viral vector (MDA+/?). The growth of MDA?/? tumor was significantly enhanced when coimplanted with wild-type MRC5 (MRC5?/?), and the stimulatory effect was reduced when MRC5+/+ cells were coimplanted instead of MRC5?/?. The reduction of tumor growth was accompanied by reduction of angiogenesis, as demonstrated by the staining of VE-cadherin in primary tumor tissues. Conclusions: Retroviral ribozyme transgenes targeting HGF/SF in fibroblasts or its receptor cMET in mammary cancer cells can reduce the growth of mammary cancer and associated angiogenesis by inhibiting paracrine stromal–tumor cell interactions.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Medicine |
Subjects: | R Medicine > R Medicine (General) |
ISSN: | 1078-0432 |
Last Modified: | 17 Oct 2022 08:25 |
URI: | https://orca.cardiff.ac.uk/id/eprint/106 |
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