American Association for Cancer Research
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Supplementary Figures from Mesenchymal CD44 Expression Contributes to the Acquisition of an Activated Fibroblast Phenotype via TWIST Activation in the Tumor Microenvironment

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posted on 2023-03-30, 21:43 authored by Erika L. Spaeth, Adam M. Labaff, Bryan P. Toole, Ann Klopp, Michael Andreeff, Frank C. Marini

PDF file, 1638K, Transgenic bone marrow transplantation into GFP+ recipient mice resulted in mice with two labeled cell populations (S1); Fewer activated myofibroblast incorporation in tumors engrafted in CD44-/- BMT mice compared to WT BMT (S2); Human and murine MSC phenotype shows no difference between knockdown MSC and naive MSC (S3); Protein and RNA expression of CD44 ligands in tumor cell lines and MSC (S4); Blocking CD44 expression on MSC inhibits migration in vitro and in vivo (S5).

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ARTICLE ABSTRACT

Tumor–stroma interactions play a crucial role in cancer progression by eliciting factors that promote proliferative, angiogenic, and invasive supports to the tumor microenvironment. Mesenchymal stromal/stem cells (MSC) contribute to stroma in part as cancer-associated fibroblasts (CAF), but a complete understanding of how MSC contribute to the tumor stroma is lacking. In this study, we show how CAF phenotypes rely upon MSC expression of the multifunctional cell surface glycoprotein CD44, a putative stem cell marker. Through bone marrow transplantation experiments in a transgenic mouse model of cancer, we determined that CD44 deficiency leads to a relative reduction in the contribution of bone marrow–derived cells to tumor stroma. CD44 attenuation in MSC limited their expression of CAF markers induced by tumor conditioning, and these MSC migrated poorly and provided weak angiogenic support compared with wild-type MSC. These defects were linked to deficiencies in the ability of CD44-attenuated MSC to transcriptionally upregulate Twist expression. Together, our results establish that CD44 expression contributes to critical functions in the tumor stroma. Cancer Res; 73(17); 5347–59. ©2013 AACR.