在 3D 培养中,整合素介导的前列腺癌细胞星状突起上趋化因子受体的表达。
Chemokine receptor expression on integrin-mediated stellate projections of prostate cancer cells in 3D culture.
机构信息
Discovery Biology, Eskitis Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia.
出版信息
Cytokine. 2013 Oct;64(1):122-30. doi: 10.1016/j.cyto.2013.07.012. Epub 2013 Aug 3.
The chemokine receptor CXCR7 has emerged as a regulator of prostate tumor growth and invasion, along with the well-established role of its closely related receptor, CXCR4, and their shared ligand, SDF-1α. Consequently, inhibition of the CXCR7/CXCR4/SDF-1α axis may assist in controlling prostate tumor growth and progression. To facilitate the development of potential therapeutics, further clarification of CXCR7 function is required, specifically in relation to CXCR4. In this study, we report that CXCR7 and CXCR4 were co-expressed in LNCaP, DU145 and PC3 cell lines in 2D culture. When cultured in 3D using Matrigel, a marked up-regulation of both receptors was observed in PC3 cells. Interestingly, both CXCR7 and CXCR4 co-localized within radiating cellular structures, termed stellate projections, which protruded outward into the matrix. The stellate projections were rich in the expression of pro-invasive integrin β1, β-laminin and MMP-11 proteins. The development of the stellate projections was mediated by integrin β1-mediated interactions with the ECM, which also regulated the expression of CXCR7 and CXCR4. Taken together, these results demonstrate that integrin-mediated cell-ECM interactions can modulate tumor cell morphology, and regulate the expression of chemokine receptors which are associated with the invasive phenotype and progression of PCa.
趋化因子受体 CXCR7 已成为前列腺肿瘤生长和侵袭的调节剂,与其密切相关的受体 CXCR4 及其共同配体 SDF-1α 的作用也得到了确立。因此,抑制 CXCR7/CXCR4/SDF-1α 轴可能有助于控制前列腺肿瘤的生长和进展。为了促进潜在治疗药物的开发,需要进一步阐明 CXCR7 的功能,特别是与 CXCR4 的关系。在这项研究中,我们报告在 2D 培养中,LNCaP、DU145 和 PC3 细胞系中共同表达 CXCR7 和 CXCR4。当在 Matrigel 中进行 3D 培养时,观察到 PC3 细胞中这两种受体的表达明显上调。有趣的是,CXCR7 和 CXCR4 均共定位在放射状细胞结构中,称为星状突起,这些突起向外突出到基质中。星状突起富含表达具有侵袭性的整合素 β1、β-层粘连蛋白和 MMP-11 蛋白。星状突起的发育是由整合素 β1 介导的与细胞外基质的相互作用介导的,这也调节了 CXCR7 和 CXCR4 的表达。总之,这些结果表明整合素介导的细胞-细胞外基质相互作用可以调节肿瘤细胞形态,并调节与 PCa 侵袭表型和进展相关的趋化因子受体的表达。