Viral vector-induced expression of bone morphogenetic protein 2 produces inhibition of tumor growth and bone differentiation of stem cells Journal Article
| Authors: | Fong, S.; Chan, M. K.; Fong, A.; Bowers, W. J.; Kelly, K. J. |
| Article Title: | Viral vector-induced expression of bone morphogenetic protein 2 produces inhibition of tumor growth and bone differentiation of stem cells |
| Abstract: | A number of hormonal factors have been shown to be instrumental in the calcification process. This study represents an attempt at using one of these factors to specifically induce calcification of tumors to arrest tumor growth. The gene encoding bone morphogenetic protein 2 (BMP-2) was placed under transcriptional control of the promoter for carcinoembryonic antigen (CEA). This gene cassette was cloned into a herpes simplex virus (HSV) amplicon vector (HSV-CEA-BMP2). This vector was used to induce local BMP-2 production in CEA-expressing tumor cells to retard cell growth. Lysates of tumor cells treated with HSV-CEA-BMP2 were applied to stem cells to determine if BMP-2 expression promotes differentiation to bone lineage. pHSV-CEA-BMP2 efficiently transduced both CEA-expressing and non-expressing cells. BMP-2 was only expressed in CEA-positive cells. BMP-2 expression led to an inhibition of tumor cell growth. BMP-2 released by these CEA-expressing tumors also drove the differentiation of mesenchymal stem cells to bone lineage. This proof-of-concept study demonstrates that tumor cells can be specifically engineered to produce BMP-2, which leads to growth retardation and to the differentiation of non-committed stem cells to bone. This Medusa effect can theoretically be exploited to retard tumor growth. © 2010 Nature Publishing Group All rights reserved. |
| Keywords: | controlled study; protein expression; human cell; cancer growth; neoplasms; antigen expression; breast cancer; carcinoembryonic antigen; cell line; cell differentiation; cell line, tumor; cell lineage; genetic vectors; sarcoma; molecular cloning; cancer inhibition; promoter regions, genetic; colon cancer; amplicon; bone; gene therapy; simplexvirus; mesenchymal stem cell; ossification; bone morphogenetic protein 2; herpes simplex virus; cell lysate; virus vector; mesenchymal stem cells |
| Journal Title: | Cancer Gene Therapy |
| Volume: | 17 |
| Issue: | 2 |
| ISSN: | 0929-1903 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2010-02-01 |
| Start Page: | 80 |
| End Page: | 85 |
| Language: | English |
| DOI: | 10.1038/cgt.2009.56 |
| PUBMED: | 19834515 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: CGTHE" - "Source: Scopus" |
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