Anti-CD44 monoclonal antibody, clone G20-55-3 [PE]

In cancer treatment, the most attractive feature of mesenchymal stem cells (MSCs) is it's homing to tumor tissues. MSC is an important part of the "colon cancer stem cell niche", but little research has been done on the tropism of human MSCs toward colon cancer stem cells (CCSCs). In this study, we first compared the effects of three tissue-derived MSCs (bone marrow, adipose tissue, and placenta) in vivo on colon tumor xenograft growth. Then, we analyzed the tropism of bone marrow-derived MSCs (BMSCs) toward normal intestinal epithelial cells (NCM460), parental colon cancer cells, CD133(-)/CD44(-,)and CD133(+)/CD44(+)colon cancer cells in vitro. Microarray analysis and in vitro experiments explored the mechanism of mediating the homing of BMSCs toward CCSCs. Compared with the parental and CD133(-)/CD44(-)colon cancer cells, CD133(+)/CD44(+)cells have a stronger ability to recruit BMSCs. In addition, BMSCs were significantly transformed into cancer-associated fibroblasts after being recruited by CCSCs. After coculture of BMSCs and CCSCs, the expression of interleukin (IL)-6, IL-8, IL-32, and CCL20 was significantly increased. Compared with parental strains, CD133(-)/CD44(-)cells, and NCM460, BMSC secreted significantly more IL-8 after coculture with CD133(+)/CD44(+)cells. Low concentration of IL-8 peptide inhibitors (100 ng/ml) and CXC receptor 2 (CXCR2) inhibitors have little effect on the migration of BMSCs, but can effectively weaken CCSC stemness and promote dormant CSCs in the coculture system to re-enter into the cell cycle. The endogenous IL-8 knockout in BMSCs or BMSCs loaded with IL-8 and/or CXCR2 inhibitors will make the therapy of BMSC targeting CCSCs function at its best.

Glioblastoma (GBM) is the most frequent and devastating primary tumor of the central nervous system with a median survival of 12 to 15 months after diagnosis. GBM is highly difficult to treat due to its delicate location, inter- and intra-tumoral heterogeneity, and high plasticity in response to treatment. In this study, we intracranially implanted primary GBM cells into mice which underwent conventional GBM treatments, including irradiation, temozolomide, and a combination. We obtained single cell suspensions through a combination of mechanical and enzymatic dissociation of brain tissue and investigated in detail the changes in GBM cells in response to conventional treatments in vivo using multi-color flow cytometry and cluster analysis. CD44 expression was elevated in all treatment groups, which was confirmed by subsequent immunohistochemistry. High CD44 expression was furthermore shown to correlate with poor prognosis of GBM and low-grade glioma (LGG) patients. Together, these results indicate a key role for CD44 in glioma pathogenesis.