Enhanced growth of tumors in SPARC null mice is associated with changes in the ECM

Rolf A. Brekken, Pauli Puolakkainen, David C. Graves, Gail Workman, Sharon R. Lubkin, E. Helene Sage

Research output: Contribution to journalArticle

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Abstract

SPARC, a 32-kDa glycoprotein, participates in the regulation of morphogenesis and cellular differentiation through its modulation of cell-matrix interactions. Major functions defined for SPARC in vitro are de-adhesion and antiproliferation. In vivo, SPARC is restricted in its expression to remodeling tissues, including pathologies such as cancer. However, the function of endogenous SPARC in tumor growth and progression is not known. Here, we report that implanted tumors grew more rapidly in mice lacking SPARC. We observed that tumors grown in SPARC null mice showed alterations in the production and organization of ECM components and a decrease in the infiltration of macrophages. However, there was no change in the levels of angiogenic growth factors in comparison to tumors grown in wild-type mice, although there was a statistically significant difference in total vascular area. Whereas SPARC did inhibit the growth of tumor cells in vitro, it did not have a demonstrable effect on the proliferation or apoptosis of tumor cells in vivo. These data indicate that host-derived SPARC is important for the appropriate organization of the ECM in response to implanted tumors and highlight the importance of ECM in regulating tumor growth.

Original languageEnglish (US)
Pages (from-to)487-495
Number of pages9
JournalJournal of Clinical Investigation
Volume111
Issue number4
DOIs
StatePublished - Feb 2003

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Growth
Neoplasms
Angiogenesis Inducing Agents
Morphogenesis
Cell Communication
Blood Vessels
Intercellular Signaling Peptides and Proteins
Glycoproteins
Macrophages
Apoptosis
Pathology
In Vitro Techniques

ASJC Scopus subject areas

  • Medicine(all)

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Enhanced growth of tumors in SPARC null mice is associated with changes in the ECM. / Brekken, Rolf A.; Puolakkainen, Pauli; Graves, David C.; Workman, Gail; Lubkin, Sharon R.; Sage, E. Helene.

In: Journal of Clinical Investigation, Vol. 111, No. 4, 02.2003, p. 487-495.

Research output: Contribution to journalArticle

Brekken, Rolf A. ; Puolakkainen, Pauli ; Graves, David C. ; Workman, Gail ; Lubkin, Sharon R. ; Sage, E. Helene. / Enhanced growth of tumors in SPARC null mice is associated with changes in the ECM. In: Journal of Clinical Investigation. 2003 ; Vol. 111, No. 4. pp. 487-495.
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