Vascular Biology Program, Department of Surgery, Karp Family Research Laboratories, Children's Hospital, Boston, MA 02115, USA.
Oncogene. 2012 May 3;31(18):2362-72. doi: 10.1038/onc.2011.406. Epub 2011 Oct 3.
Collagen XXIII is a transmembrane collagen previously shown to be upregulated in metastatic prostate cancer that has been used as a tissue and fluid biomarker for non-small cell lung cancer and prostate cancer. To determine whether collagen XXIII facilitates cancer cell metastasis in vivo and to establish a function for collagen XXIII in cancer progression, collagen XXIII knockdown cells were examined for alterations in in vivo metastasis as well as in vitro cell adhesion. In experimental and spontaneous xenograft models of metastasis, H460 cells expressing collagen XXIII shRNA formed fewer lung metastases than control cells. Loss of collagen XXIII in H460 cells also impaired cell adhesion, anchorage-independent growth and cell seeding to the lung, but did not affect cell proliferation. Corroborating a role for collagen XXIII in cell adhesion, overexpression of collagen XXIII in H1299 cells, which do not express endogenous collagen XXIII, enhanced cell adhesion. Consequent reduction in OB-cadherin, alpha-catenin, gamma-catenin, beta-catenin, vimentin and galectin-3 protein expression was also observed in response to loss of collagen XXIII. This study suggests a potential role for collagen XXIII in mediating metastasis by facilitating cell-cell and cell-matrix adhesion as well as anchorage-independent cell growth.
胶原 XXIII 是一种跨膜胶原，先前已被证明在转移性前列腺癌中上调，已被用作非小细胞肺癌和前列腺癌的组织和液体生物标志物。为了确定胶原 XXIII 是否在体内促进癌细胞转移，并确定胶原 XXIII 在癌症进展中的功能，研究了胶原 XXIII 敲低细胞在体内转移以及体外细胞黏附方面的变化。在转移性实验和自发异种移植模型中，表达胶原 XXIII shRNA 的 H460 细胞比对照细胞形成的肺转移灶更少。H460 细胞中胶原 XXIII 的缺失也损害了细胞黏附、无锚定生长和细胞在肺部的播种，但不影响细胞增殖。胶原 XXIII 在细胞黏附中的作用得到了证实，在不表达内源性胶原 XXIII 的 H1299 细胞中过表达胶原 XXIII 增强了细胞黏附。随后还观察到，由于胶原 XXIII 的缺失，OB-钙粘蛋白、α-连环蛋白、γ-连环蛋白、β-连环蛋白、波形蛋白和半乳糖凝集素-3 蛋白的表达减少。这项研究表明，胶原 XXIII 通过促进细胞-细胞和细胞-基质黏附和无锚定生长，在介导转移中可能发挥作用。
