Wang Jun, Levenson Anait S, Satcher Robert L
Department of Orthopaedic Surgery, and Robert H. Lurie Comprehensive Cancer Center, The Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Int J Mol Med. 2006 May;17(5):849-56.
The interaction between prostate cancer cells and bone marrow stromal cells (BMSC) is critical for survival and proliferation of metastatic cancer cells in the bone microenvironment. In order to study molecular mechanisms of prostate cancer bone metastasis, we established a novel heterotypic co-culture system, in which the role of direct cell-cell contact between prostate cancer cells and BMSC in addition to soluble factors can be analyzed. Using both bi-compartmental (insert) system and heterotypic (contact) system, we identified gene expression profiles of interaction between prostate cancer and bone cells. Analysis of differential gene expressions in these two co-culture systems revealed three distinctive sets of genes: 1) genes that were modified only by soluble factors; 2) genes that were regulated by both soluble factors and physical contact; and 3) genes that were altered only by physical contact. The last group consisted of specific set of genes including collagen III, IV, X, XII, integrin alpha1, alpha2, MMP-2, MMP-9, uPA, biglycan, osteopontin and raf-1 in PC3, and collagen VIII, IX, BMP6, TGFbeta1, Smad6 and Twist in BMSC. Among genes that were modified by both soluble factors and physical contact, the gene expression was affected in the same direction (such as MKK4) or in the opposite direction (such as TGFbeta receptor 3). Overall, this suggests that heterotypic cell-cell contact may act as an independent factor affecting the progression of bone metastasis.
前列腺癌细胞与骨髓基质细胞（BMSC）之间的相互作用对于骨微环境中转移性癌细胞的存活和增殖至关重要。为了研究前列腺癌骨转移的分子机制，我们建立了一种新型的异型共培养系统，在该系统中，可以分析前列腺癌细胞与BMSC之间直接的细胞间接触以及可溶性因子的作用。使用双室（插入）系统和异型（接触）系统，我们确定了前列腺癌与骨细胞之间相互作用的基因表达谱。对这两种共培养系统中差异基因表达的分析揭示了三组不同的基因：1）仅由可溶性因子修饰的基因；2）由可溶性因子和物理接触共同调节的基因；3）仅由物理接触改变的基因。最后一组包括特定的基因集，在PC3细胞中有III型、IV型、X型、XII型胶原蛋白、整合素α1、α2、基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）、尿激酶型纤溶酶原激活物（uPA）、双糖链蛋白聚糖、骨桥蛋白和raf-1，在BMSC细胞中有VIII型、IX型胶原蛋白、骨形态发生蛋白6（BMP6）、转化生长因子β1（TGFbeta1）、Smad6和Twist。在由可溶性因子和物理接触共同修饰的基因中，基因表达受到相同方向（如MKK4）或相反方向（如TGFbeta受体3）的影响。总体而言，这表明异型细胞间接触可能作为影响骨转移进展的独立因素。
