Al-Toub Mashael, Almohawes Mohammad, Vishnubalaji Radhakrishnan, Alfayez Musaad, Aldahmash Abdullah, Kassem Moustapha, Alajez Nehad M
1Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, 11461 Saudi Arabia.
2College of Applied Medical Sciences, King Saud University, Riyadh, 11461 Saudi Arabia.
Cell Death Discov. 2019 Apr 11;5:87. doi: 10.1038/s41420-019-0169-3. eCollection 2019.
The interaction between cancer cells and molecular cues provided by tumor stromal cells plays a crucial role in cancer growth and progression. We have recently reported that the outcome of interaction between tumor cells and stromal cells is dependent on the gene expression signature of tumor cells. In the current study, we observed that several cancer cell lines, e.g., MCF7 breast cancer line, exhibited growth advantage when cultured in the presence of conditioned media (CM) derived from human bone marrow stromal stem cells (hBMSCs). Regarding the underlying molecular mechanism, we have identified CXCR7 as highly expressed by MCF7 cells and that it mediated the enhanced growth in response to hBMSC CM. Regarding the clinical relevance, we found an inverse correlation between the level of tumor gene expression of CXCR7 in bladder, breast, cervical, kidney, liver, lung, pancreatic, stomach, and uterine cancers, and patients' overall survival. Interestingly, significant positive correlation between CXCR7 and CXCL12 gene expression (Pearson = 0.3, = 2.0 × 10) was observed in breast cancer patients, suggesting a biological role for the CXCR7/CXCL12 genetic circuit in breast cancer biology. Our data provide insight into the molecular mechanisms by which stromal-derived microenvironmental cues mediate CXCR7 signaling and growth enhancement of breast cancer cells. Therapeutic targeting of this circuit might provide novel therapeutic opportunity for breast cancer.
癌细胞与肿瘤基质细胞提供的分子信号之间的相互作用在癌症的生长和进展中起着至关重要的作用。我们最近报道，肿瘤细胞与基质细胞之间相互作用的结果取决于肿瘤细胞的基因表达特征。在当前的研究中，我们观察到几种癌细胞系，例如MCF7乳腺癌细胞系，在存在源自人骨髓基质干细胞（hBMSCs）的条件培养基（CM）的情况下培养时表现出生长优势。关于潜在的分子机制，我们已确定CXCR7在MCF7细胞中高表达，并且它介导了对hBMSC CM的反应中生长的增强。关于临床相关性，我们发现膀胱、乳腺、宫颈、肾、肝、肺、胰腺、胃和子宫癌中CXCR7的肿瘤基因表达水平与患者的总生存期呈负相关。有趣的是，在乳腺癌患者中观察到CXCR7和CXCL12基因表达之间存在显著正相关（Pearson = 0.3， = 2.0×10），这表明CXCR7/CXCL12基因回路在乳腺癌生物学中具有生物学作用。我们的数据为基质衍生的微环境信号介导CXCR7信号传导和乳腺癌细胞生长增强的分子机制提供了见解。对该回路的治疗性靶向可能为乳腺癌提供新的治疗机会。
