Enhanced growth of tumors in SPARC null mice is associated with changes in the ECM
Rolf A. Brekken, … , Sharon R. Lubkin, E. Helene Sage
Rolf A. Brekken, … , Sharon R. Lubkin, E. Helene Sage
Published February 15, 2003
Citation Information: J Clin Invest. 2003;111(4):487-495. https://doi.org/10.1172/JCI16804.
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Article Oncology

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

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 the ECM in regulating tumor growth.

Authors

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

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Tumor growth is enhanced in SPARC null mice. SP+/+ and SP–/– mice were i...
Tumor growth is enhanced in SPARC null mice. SP+/+ and SP–/– mice were injected subcutaneously with 2 × 106 LLC or 1 × 106 EL4 cells (a and c, respectively). (a) Comparison of the mean final volume and weight of LLC tumors grown subcutaneously in SP+/+ and SP–/– mice. The results shown are the combination of two independent experiments, which lasted 24–29 days after tumor cell injection. (b) Comparison of the number of lung surface tumor colonies in age-matched SP+/+ and SP–/– mice 14–19 days after intravenous injection of 1 × 105 LLC cells. The results shown are the combination of two independent experiments. Surface lung tumor colonies were visualized under a dissecting microscope after fixation in Bouin’s fixative. (c) Comparison of the mean final volume and weight of EL4 tumors grown subcutaneously in SP+/+ and SP–/– mice. The results shown are the combination of two independent experiments, which lasted 14–16 days after tumor cell injection. (d) Comparison of the animals’ weights after intraperitoneal injection of 1 × 106 EL4 cells, and the weight of the GI tract at sacrifice. P values were determined by Student’s t test.