New Insights Into Implementation of Mesenchymal Stem Cells in Cancer Therapy: Prospects for Anti-angiogenesis Treatment

Abstract

Tumor microenvironment interacts with tumor cells, establishing an atmosphere to contribute or suppress the tumor development. Among the cells which play a role in the tumor microenvironment, mesenchymal stem cells (MSCs) have been demonstrated to possess the ability to orchestrate the fate of tumor cells, drawing the attention to the field. MSCs have been considered as cells with double-bladed effects, implicating either tumorigenic or anti-tumor activity. On the other side, the promising potential of MSCs in treating human cancer cells has been observed from the clinical studies. Among the beneficial characteristics of MSCs is the natural tumor-trophic migration ability, providing facility for drug delivery and, therefore, targeted treatment to detach tumor and metastatic cells. Moreover, these cells have been the target of engineering approaches, due to their easily implemented traits, in order to obtain the desired expression of anti-angiogenic, anti-proliferative, and pro-apoptotic properties, according to the tumor type. Tumor angiogenesis is the key characteristic of tumor progression and metastasis. Manipulation of angiogenesis has become an attractive approach for cancer therapy since the introduction of the first angiogenesis inhibitor, namely bevacizumab, for metastatic colorectal cancer therapy. This review tries to conclude the approaches, with focus on anti-angiogenesis approach, in implementing the MSCs to combat against tumor cell progression.

ERK/MAPK signalling pathway and tumorigenesis (Review)

“…In the absence of blood vessels, tumour tissues rarely exceed 2 mm 3 (116); blood vessels are also the channels through which tumour metastasis occurs (117). Tumour angiogenesis involves not only the overexpression of angiogenic factors, but also the low expression of angiogenic inhibitors and an imbalance between the two (118). VEGF is an important pro-angiogenic factor and the most powerful pro-vascular endothelial growth cytokine that promotes cell division and vascular construction from esophageal cancer and ovarian cancer, increases microvascular permeability and promotes endothelial cell migration (119)(120)(121).…”

Resistance Mechanisms to Anti-angiogenic Therapies in Cancer

“…Also, the regression in tumor vasculature and the reduction in blood flow that result from AIs would impede the delivery of chemotherapeutic agents into tumors. All these complications of AI use would allow for tumor metastasis and would hence serve as practical limitations to drug development (309).…”

“…In addition, in the light of the wide gap between our improving knowledge in the mechanobiology of MSCs and our satisfactory understanding of their clinical implications, novel approaches should be suggested to fill the gap. This could be made possible by engineering MSCs to selectively deliver antiangiogenic molecules (309).…”

ADAM8 affects glioblastoma progression by regulating osteopontin-mediated angiogenesis

“…In 2009, the FDA approved bevacizumab, a drug targeting neovascular formation, for patients with recurrent glioblastomas (Davis 2016). Neo-angiogenesis is critical for tissue growth and repair, and forms the basis for tumor progression (Javan et al 2019;Viallard and Larrivee 2017). Thus, anti-angiogenic drugs have been widely suggested for clinical cancer treatment.…”