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Stromelysin-3 suppresses tumor cell apoptosis in a murine model.

Publication ,  Journal Article
Wu, E; Mari, BP; Wang, F; Anderson, IC; Sunday, ME; Shipp, MA
Published in: J Cell Biochem
2001

Stromelysin-3 (STR-3) is a matrix metalloproteinase with a unique pattern of expression and substrate specificity. During embryogenesis and remodeling of normal adult tissues, STR-3 is produced by stromal cells in direct contact with epithelial cells undergoing regional apoptosis and selective cell survival. STR-3 is also overexpressed by interdigitating stromal cells in primary epithelial malignancies. Although STR-3 does not degrade classic extracellular matrix components, the enzyme promotes the establishment of local tumors in nude mice by as yet undefined mechanisms. STR-3 is induced when malignant epithelial cells come into contact with surrounding stromal elements; the active stromal cell-derived 45 kDa enzyme is subsequently processed to a 35 kDa protein without enzymatic activity. We have generated MCF-7 transfectants expressing wild type or catalytically inactive 45 kDa STR-3 (STR-3wt and STR-3cat-) or secreted 35 kDa STR-3 (35 kDa STR-3sec) and evaluated their implantation and survival in nude mice. Tumors developed significantly more rapidly in animals receiving STR-3wt, rather than vector-only, STR-3cat- or 35 kDa STR-3sec transfectants. Most importantly, STR-3wt tumors had a significantly lower percentage of apoptotic cells than tumors derived from vector-only, STR-3cat- or 35 kDa STR-3sec transfectants. Taken together, these studies suggest that the active STR-3 enzyme may increase tumor take by suppressing tumor cell apoptosis and that 45 kDa to 35 kDa STR-3 processing limits STR-3 activity at the tumor/stromal interface. Because STR-3 is secreted as an active enzyme rather than a proform, subsequent 45 kDa to 35 kDa STR-3 processing may represent a novel mechanism for regulating enzymatic activity.

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Published In

J Cell Biochem

DOI

ISSN

0730-2312

Publication Date

2001

Volume

82

Issue

4

Start / End Page

549 / 555

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transfection
  • Neoplasms
  • Neoplasm Transplantation
  • Mutation
  • Mice, Nude
  • Mice
  • Metalloendopeptidases
  • Matrix Metalloproteinase 11
  • Humans
 

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Wu, E., Mari, B. P., Wang, F., Anderson, I. C., Sunday, M. E., & Shipp, M. A. (2001). Stromelysin-3 suppresses tumor cell apoptosis in a murine model. J Cell Biochem, 82(4), 549–555. https://doi.org/10.1002/jcb.1181
Wu, E., B. P. Mari, F. Wang, I. C. Anderson, M. E. Sunday, and M. A. Shipp. “Stromelysin-3 suppresses tumor cell apoptosis in a murine model.J Cell Biochem 82, no. 4 (2001): 549–55. https://doi.org/10.1002/jcb.1181.
Wu E, Mari BP, Wang F, Anderson IC, Sunday ME, Shipp MA. Stromelysin-3 suppresses tumor cell apoptosis in a murine model. J Cell Biochem. 2001;82(4):549–55.
Wu, E., et al. “Stromelysin-3 suppresses tumor cell apoptosis in a murine model.J Cell Biochem, vol. 82, no. 4, 2001, pp. 549–55. Pubmed, doi:10.1002/jcb.1181.
Wu E, Mari BP, Wang F, Anderson IC, Sunday ME, Shipp MA. Stromelysin-3 suppresses tumor cell apoptosis in a murine model. J Cell Biochem. 2001;82(4):549–555.
Journal cover image

Published In

J Cell Biochem

DOI

ISSN

0730-2312

Publication Date

2001

Volume

82

Issue

4

Start / End Page

549 / 555

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transfection
  • Neoplasms
  • Neoplasm Transplantation
  • Mutation
  • Mice, Nude
  • Mice
  • Metalloendopeptidases
  • Matrix Metalloproteinase 11
  • Humans