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Background: Desmoid tumors (DTs) are nonmalignant neoplasms of mesenchymal origin that largely contain cells of fibroblast lineage. These tumors occur in ~30% of Familial Adenomatous Polyposis Coli (FAP) patients with germline mutations in the Adenomatous Polyposis Coli (APC) gene. Sporadic DTs are rare and contain mutations in the CTNNB1 gene, which like APC, regulates Wnt signaling. Emerging data implicate multipotent mesenchymal stromal cells (MSCs) in the origin of mesenchymal tumors. During wound healing, MSCs are recruited to sites of tissue injury, and are associated with post-surgical scars.
Methods/Results: We studied 16 DTs of FAP-associated and sporadic cases. All tumors expressed stem cell markers, CD73, CD90, and BMI-1, while matching normal stromal tissues were negative for these antigens. DTs also contained CD34+CD105+ALK1+ fibrocytes, which are linked to wound healing and contribute to angiogenesis and fibrosis. We derived a MSC cell line from a FAP-associated DT. Cytochemistry confirmed loss of APC+ protein and expression of BMI-1. By FACS analysis, these cells were CD73+, CD90+, and CD105+, but CD34-. Upon growth in differentiation media, these cells co-expressed chondrocyte markers: CTGF, SOX9, with Alcian blue staining; adipocyte markers: PPAR?, c/EPB?, with Oil Red O staining; and osteocyte markers: OPN, RUNX2, with von Kossa staining.
Conclusion: These results suggest that DTs maintain MSCs in wound healing settings with deregulated Wnt signaling produced by APC loss. The differentiation potential of these cells, combined with expression of BMI-1, a transcriptional repressor downstream of Hedgehog and Notch signaling, suggests that DTs may respond to therapy targeting these pathways.