Identification and Characterization of Hematopoietic Stem (HSC)/Progenitor Cells in Human Solid Tumors

It has recently been shown that a solid tumor recruits cells to the tumor mass, which facilitate vascularization, suppress immune responses, aid its growth, and influence metastatic potential. These recruited cells include mesenchymal stem cells, endothelial progenitor cells and tumor infiltrating leukocytes. By performing multiparameter FACS analysis on primary lung carcinoma and pleural effusion material, we demonstrate for the first time the consistent presence of CD45⁺/CD34⁺ cells (mean 1.6% of total CD45⁺cells range 0.24–13.2% n=12). In primary tumor samples, CD45⁺ lymphohematopoietic cells were purified by the MACS system and examined for progenitor colony formation in methycellulose. Erythroid and myeloid colony formation was observed in the CD45⁺ selected subfraction. We assayed for HSC activity by cobblestone formation (CAFC) on MS-5 stroma. Week 2 and week 5 CAFC potential was present in CD45⁺ purified ovarian cancer ascites. In non-irradiated NOD/SCID IL2 gamma null mice injected subcutaneously with dissociated and unfractionated lung tumor and ovarian peritoneal ascites, small numbers of human CD45⁺ cells were recovered from the bone marrow after 2–3 months which gave rise to hematopoietic colonies. Human CD45⁺ cells also persisted within the retransplanted subcutaneous tumors. In conclusion, we report the recruitment of HSCs and progenitors to primary tumor sites. The differentiation and self-renewal potential of these HSCs indicate a potential alternative source of tumor-infiltrating leukocytes as opposed to or in addition to recruitment of mature cells from the circulation.

The role of solid tumors in mobilizing HSCs and progenitors from the bone marrow and their selective chemotaxis to the primary and metastatic sites require further investigation. Targeting this novel tumor-HSC interaction may offer new therapeutic opportunities for controlling tumor growth and metastasis.