The various stromal cell types that constitute the tumor microenvironment may be recruited from adjacent normal tissue—the most obvious reservoir of such cell types. However, in recent years, the bone marrow has increasingly been implicated as a key source of tumor-associated stromal cells. Mesenchymal stem and progenitor cells have been found to transit into tumors from the marrow, where they may differentiate into the various well-characterized stromal cell types. Some of these recent arrivals may also persist in an undifferentiated or partially differentiated state, exhibiting functions that their more differentiated progeny lack.
The bone marrow origins of stromal cell types have been demonstrated using tumor-bearing mice in which the bone marrow cells and thus their disseminated progeny have been selectively labeled with reporters such as green fluorescent protein (GFP). While immune inflammatory cells have been long known to derive from the bone marrow, more recently the progenitors of pericytes and of various subtypes of cancer-associated fibroblasts originating from the bone marrow have been described in various mouse models of cancer; the prevalence and functional importance of endothelial progenitors for tumor angiogenesis is currently unresolved. Taken together, these various lines of evidence indicate that tumor-associated stromal cells may be supplied to growing tumors by proliferation of preexisting stromal cells, by differentiation in situ of local stem/progenitor cells originating in the neighboring normal tissue, or via recruitment of bone marrow-derived stem/progenitor cells.