How Signaling Molecules Regulate Tumor Microenvironment: Parallels to Wound Repair

Abstract

It is now suggested that the inhibition of biological programs that are associated with the tumor microenvironment may be critical to the diagnostics, prevention and treatment of cancer. On the other hand, a suitable wound microenvironment would accelerate tissue repair and prevent extensive scar formation. In the present review paper, we define key signaling molecules (growth factors, cytokines, chemokines, and galectins) involved in the formation of the tumor microenvironment that decrease overall survival and increase drug resistance in cancer suffering patients. Additional attention will also be given to show whether targeted modulation of these regulators promote tissue regeneration and wound management. Whole-genome transcriptome profiling, in vitro and animal experiments revealed that interleukin 6, interleukin 8, chemokine (C-X-C motif) ligand 1, galectin-1, and selected proteins of the extracellular matrix (e.g., fibronectin) do have similar regulation during wound healing and tumor growth. Published data demonstrate remarkable similarities between the tumor and wound microenvironments. Therefore, tailor made manipulation of cancer stroma can have important therapeutic consequences. Moreover, better understanding of cancer cell-stroma interaction can help to improve wound healing by supporting granulation tissue formation and process of reepithelization of extensive and chronic wounds as well as prevention of hypertrophic scars and formation of keloids.

Cancer-Associated Fibroblasts Promote the Chemo-resistance in Gastric Cancer through Secreting IL-11 Targeting JAK/STAT3/Bcl2 Pathway

“…In tumor microenvironment, cytokines are often characterized as functional redundancy and tissue-specific activities [20,21]. Current studies have shown that over-activated IL-11 contributed to the activation of the gp130 through binding to its receptor in solid tumors [6,11], which afterwards activated JAK/STAT3 pathway that was involved in regulating angiogenesis, metastasis, resistance to apoptosis, cell proliferation, and immune evasion [22].…”

Tumour growth and immune evasion as targets for a new strategy in advanced cancer

“…Soluble mediators, mainly growth factors, cytokines and chemokines, in addition to host immune cells are also produced by cancer-associated fibroblasts (CAFs) or by tumour cells themselves. Several growth factors, namely TGF-β, insulin-like growth factor 2 (IGF-2) and vascular endothelial growth factor (VEGF), cytokines, namely IL-1, IL-4, IL-6, IL-8, IL-10 and tumournecrosis factor alpha, chemokines, namely chemokine (C-X-C motif) ligand 1 and C-C motif chemokine receptor 7, have been reported to be closely involved in tumour progression, invasion and immune escape (Eftekhari et al 2017, Gál et al 2017, Setrerrahmane & Xu 2017 and are potential targets for anti-tumour therapies. Moreover, cancer cells not only express these soluble mediators but also frequently overexpress the related receptors to escape from the immune responses (Setrerrahmane & Xu 2017).…”

Advances in Proteomic Techniques for Cytokine Analysis: Focus on Melanoma Research

“…Bead-based and planar antibody arrays have been utilized or are potentially applicable to a wide range of cancer studies, including search for diagnostic and prognostic biomarkers, evaluation of antitumour treatment efficacy, understanding of the biology underlining tumourigenesis and tumour progression [ 123 , 135 , 136 ], including mapping the role of tumour microenvironment and inter-cellular cross-talk [ 137 ].…”