Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment

Abstract

Mutationally corrupted cancer (stem) cells are the driving force of tumor development and progression. Yet, these transformed cells cannot do it alone. Assemblages of ostensibly normal tissue and bone marrow-derived (stromal) cells are recruited to constitute tumorigenic microenvironments. Most of the hallmarks of cancer are enabled and sustained to varying degrees through contributions from repertoires of stromal cell types and distinctive subcell types. Their contributory functions to hallmark capabilities are increasingly well understood, as are the reciprocal communications with neoplastic cancer cells that mediate their recruitment, activation, programming, and persistence. This enhanced understanding presents interesting new targets for anticancer therapy.

Engineering a Tumor Microenvironment‐Mimetic Niche for Tissue Regeneration with Xenogeneic Cancer Cells

“…The tumor could tactically solve this dilemma thanks to its unique TME with two distinctive features—pro‐tumor growth and immunosuppressive 17, 18, 46, 47. Thus, we assumed that re‐creation of analogous TME would provide the proper ground to support xenograft cells to grow in the host body.…”

Microvesicle-delivery miR-150 promotes tumorigenesis by up-regulating VEGF, and the neutralization of miR-150 attenuate tumor development

“…Previous studies have shown that tumors consist not only of malignant cells but also of various stromal cell types (Lewis et al, 1995;Hanahan and Coussens, 2012). The stromal cells in cancer can be divided into three subtypes: angiogenic vascular cells (AVCS), infi ltrating immune cells (IICs), and cancer-associated fi broblastic cells (CAFs) (Hanahan and Coussens, 2012).…”

“…Previous studies have shown that tumors consist not only of malignant cells but also of various stromal cell types (Lewis et al, 1995;Hanahan and Coussens, 2012). The stromal cells in cancer can be divided into three subtypes: angiogenic vascular cells (AVCS), infi ltrating immune cells (IICs), and cancer-associated fi broblastic cells (CAFs) (Hanahan and Coussens, 2012). Tumor growth is clearly dependent on angiogenesis, as tumors need to establish a blood vessel network to access oxygen and nutrients (Millan Nunez-Cortes, 1991;Cristofanilli et al, 2002;Folkman, 2007).…”

From sentinel cells to inflammatory culprits: cancer‐associated fibroblasts in tumour‐related inflammation

“…While the distinct functional characteristics of the various CAF subsets are poorly defined, their role in supporting tumour growth has been established: CAFs have been found to promote tumour growth by directly stimulating tumour cell proliferation via secreted growth factors, and by enhancing angiogenesis [17][18][19]. Enhancement of tumour angiogenesis by CAFs can be mediated either directly, by secreting pro-angiogenic factors including interleukin (IL)-8/CXCL8, vascular endothelial growth factor (VEGF), and fibroblast growth factor (FGF)-2, or indirectly, by secreting extracellular matrix (ECM)-remodelling proteases, such as matrix metalloproteinase (MMP)-9, MMP-13, and MMP-14 that activate a multitude of latent soluble and insoluble factors with diverse activities [7,[20][21][22]. In addition, CAFs foster tumour progression and metastasis by modifying the architecture of the ECM, by enhancing deposition of collagen, and by mediating increased cross-linking of collagen fibres, thus stiffening stroma.…”