Multipotent mesenchymal stromal cells promote tumor growth in distinct colorectal cancer cells by a β1‐integrin‐dependent mechanism. Issue 4 (1st October 2015)

• Record Type: Journal Article
• Authors: Widder, Miriam; Lützkendorf, Jana; Caysa, Henrike; Unverzagt, Susanne; Wickenhauser, Claudia; Benndorf, Ralf A.; Schmoll, Hans‐Joachim; Müller‐Tidow, Carsten; Müller, Thomas; Müller, Lutz P.
• Is Part Of: International journal of cancer. Volume 138:Issue 4(2016:Feb. 15)
• Page Start: 964
• Page End: 975
• Publication Date: 2015-10-01
• Subjects: tumor‐stroma‐interactions -- MSC -- CRC -- β1‐integrin -- growth promotion; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.29844
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Tumor–stroma interactions play an essential role in the biology of colorectal carcinoma (CRC). Multipotent mesenchymal stromal cells (MSC) may represent a pivotal part of the stroma in CRC, but little is known about the specific interaction of MSC with CRC cells derived from tumors with different mutational background. In previous studies we observed that MSC promote the xenograft growth of the CRC cell‐line DLD1. In the present study, we aimed to analyze the mechanisms of MSC‐promoted tumor growth using various in vitro and in vivo experimental models and CRC cells of different mutational status. MSC specifically interacted with distinct CRC cells and supported tumor seeding in xenografts. The MSC–CRC interaction facilitated three‐dimensional spheroid formation in CRC cells with dysfunctional E‐cadherin system. Stable knock‐downs revealed that the MSC‐facilitated spheroid formation depended on β1‐integrin in CRC cells. Specifically in α‐catenin‐deficient CRC cells this β1‐integrin‐dependent interaction resulted in a MSC‐mediated promotion of early tumor growth in vivo . Collagen I and other extracellular matrix compounds were pivotal for the functional MSC–CRC interaction. In conclusion, our data demonstrate a differential interaction of MSC with CRC cells of different mutational background. Our study is the first to show that MSC specifically compared to normal fibroblasts impact early xenograft growth of distinct α‐catenin deficient CRC cells possibly through secretion of extracellular matrix. This mechanism could serve as a future target for therapy and metastasis prevention. Abstract : What's new? Tumor–stroma interactions play an essential role in colorectal carcinoma (CRC), with multipotent mesenchymal stromal cells (MSC) possibly representing a key part of the stroma. However, little is known about specific interactions between MSC and CRC cells with different mutational backgrounds. This study shows that MSC facilitates tumor formation in CRC cells with dysfunctional E‐cadherin in a mechanism dependent on CRC cell expressed β1‐integrin. MSC‐expressed extracellular matrix seems pivotal for this MSC–CRC interaction. In α‐catenin‐deficient CRC cells, β1‐integrin‐dependent interaction resulted in promotion of early tumor growth in vivo . The data show that MSC specifically interact with CRC cells of distinct mutational backgrounds.