Mesenchymal Stem Cells in Gastric Cancer: Vicious but Hopeful

Abstract

Tumor progression depends on the collaborative interactions between tumor cells and the surrounding stroma. First-line therapies direct against cancer cells may not reach a satisfactory outcome, such as gastric cancer (GC), with high risk of recurrence and metastasis. Therefore, novel treatments and drugs target the effects of stroma components are to be promising alternatives. Mesenchymal stem cells (MSC) represent the decisive components of tumor stroma that are found to strongly affect GC development and progression. MSC from bone marrow or adjacent normal tissues express homing profiles in timely response to GC-related inflammation signals and anchor into tumor bulks. Then the newly recruited “naïve” MSC would achieve phenotype and functional alternations and adopt the greater tumor-supporting potential under the reprogramming of GC cells. Conversely, both new-comers and tumor-resident MSC are able to modulate the tumor biology via aberrant activation of oncogenic signals, metabolic reprogramming and epithelial-to-mesenchymal transition. And they also engage in remodeling the stroma better suited for tumor progression through immunosuppression, pro-angiogenesis, as well as extracellular matrix reshaping. On the account of tumor tropism, MSC could be engineered to assist earlier diagnosis of GC and deliver tumor-killing agents precisely to the tumor microenvironment. Meanwhile, intercepting and abrogating vicious signals derived from MSC are of certain significance for the combat of GC. In this review, we mainly summarize current advances concerning the reciprocal metabolic interactions between MSC and GC and their underlying therapeutic implications in the future.

The cross talk between gastric cancer stem cells and the immune microenvironment: a tumor-promoting factor

“…In agreement with this theory, recent studies confirm that BM-MSCs promote gastric cancer progression, cell migration and tumorigenesis via c-Myc upregulation, a transcription factor involved in cell proliferation [21]. This mesenchymal stem cell (MSC) migration is dependent on chemotactic signals from GC, for example CXCL12 and TNF-α cytokines, a characteristic of MSC recently explored for cancer therapy to act as drug delivery tool or as an immune modulator [22]. Despite the aforementioned, MSCs have a dual role in many cancer types including GC, where MSCs can promote stemness, tumor growth, migration, and angiogenic activities, but have also been shown to induce inhibition of those tumorigenic activities; the role of this subset depends on the MSC model (amniotic, umbilical cord or bone marrow MSC origin) and the gastric cancer cell line used for experimental assays [23].…”

The Role of Mesenchymal Stem/Stromal Cells in Head and Neck Cancer – Regulatory Mechanisms of Tumorigenic and Immune Activity, Chemotherapy Resistance, and Therapeutic Benefits of the Use of Stromal Cell-Based Pharmacological Strategies

“…Unfortunately, the primary role of MSCs in the initiation of carcinogenesis and subsequent stages of tumour development has not been fully elucidated; despite this, a few studies indicate that MSCs have a positive impact on the inhibition of cancer lesions by activating anti-cancer mechanisms [84][85][86]. Indeed, numerous recent studies indicate that cancer-associated MSCs appear to have dual effects on tumour progression in various in vitro and animal or in vivo neoplastic models, and the pleiotropic effects of MSCs may therefore confer pro-or anti-tumour functions to cells in the tumour microenvironment [38,52,87,88].…”

Mesenchymal Stem Cell-Derived Exosomes Modulate Angiogenesis in Gastric Cancer

“…MSCs increase tumor angiogenesis within the first 14 days—the earliest stage of tumor development [ 26 ]. The trans-differentiation of GC-MSCs into endothelial cells also modifies the entire GC vascular network [ 27 ].…”