Enhanced growth of tumors in SPARC null mice is associated with changes the ECM
Enhanced growth of tumors in SPARC null mice is associated with changes the ECM
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DOI：
10.1172/jci200316804
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发表时间：
2003-02-01
影响因子：
15.9
通讯作者：
Sage, EH
中科院分区：
文献类型：
--
作者：
Brekken, RA;Puolakkainen, P;Sage, EH
SPARC 是一种 32 kDa 糖蛋白，通过调节细胞-基质相互作用参与形态发生和细胞分化的调节。 SPARC 体外定义的主要功能是脱粘和抗增殖。在体内，SPARC 的表达仅限于重塑组织，包括癌症等病理组织。然而，内源性 SPARC 在肿瘤生长和进展中的功能尚不清楚。在这里，我们报告说，缺乏 SPARC 的小鼠中植入的肿瘤生长得更快。我们观察到，在 SPARC 无效小鼠中生长的肿瘤显示 ECM 成分的产生和组织发生改变，并且巨噬细胞浸润减少。然而，与野生型小鼠中生长的肿瘤相比，血管生成生长因子的水平没有变化，尽管总血管面积存在统计学上的显着差异。虽然SPARC在体外确实抑制肿瘤细胞的生长，但它在体内对肿瘤细胞的增殖或凋亡没有明显的影响。这些数据表明，宿主来源的 SPARC 对于 ECM 响应植入肿瘤的适当组织非常重要，并强调了 ECM 在调节肿瘤生长中的重要性。
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.