Mesenchymal stromal cells induce inhibitory effects on hepatocellular carcinoma through various signaling pathways

Abstract

Hepatocellular carcinoma (HCC) is the most prevalent type of malignant liver disease worldwide. Molecular changes in HCC collectively contribute to Wnt/β-catenin, as a tumor proliferative signaling pathway, toll-like receptors (TLRs), nuclear factor-kappa B (NF-κB), as well as the c-Jun NH2-terminal kinase (JNK), predominant signaling pathways linked to the release of tumor-promoting cytokines. It should also be noted that the Hippo signaling pathway plays an important role in organ size control, particularly in promoting tumorigenesis and HCC development. Nowadays, mesenchymal stromal cells (MSCs)-based therapies have been the subject of in vitro, in vivo, and clinical studies for liver such as cirrhosis, liver failure, and HCC. At present, despite the importance of basic molecular pathways of malignancies, limited information has been obtained on this background. Therefore, it can be difficult to determine the true concept of interactions between MSCs and tumor cells. What is known, these cells could migrate toward tumor sites so apply effects via paracrine interaction on HCC cells. For example, one of the inhibitory effects of MSCs is the overexpression of dickkopf-related protein 1 (DKK-1) as an important antagonist of the Wnt signaling pathway. A growing body of research challenging the therapeutic roles of MSCs through the secretion of various trophic factors in HCC. This review illustrates the complex behavior of MSCs and precisely how their inhibitory signals interface with HCC tumor cells.

The role of mesenchymal stromal cells in immune modulation of COVID-19: focus on cytokine storm

“…Mesenchymal stromal cells (MSCs) are the cells with the unique ability to exert suppressive and regulatory effects on the immune system [15]. MSCs have been the focus of research because evidence has indicated that MSCs are able to migrate to and return from damaged tissues, exercise potent anti-inflammatory and immune regulatory activities, support the regeneration and repair of tissues, resist against apoptosis, inhibit tissue fibrosis, and decrease tissue injury [16].…”

“…On the other hand, inflammation leads to nuclear factor-kappa B (NF-κB) and c-Jun NH2-terminal kinase (JNK) signaling, which is also controlled through the factors secreted by MSCs. In addition, lung damage improves during the response of MSCs to oxidative stress, cytoprotection, and phosphoinositide 3-kinase/protein kinase B (P13K / Akt) signaling pathway [25]. Administration of BM-MSCs alleviated lung injury in a preclinical study via potentiating the PI3K/Akt signaling pathway [26,27].…”

Melatonin and Mesenchymal Stem Cells as a Key for Functional Integrity for Liver Cancer Treatment

“…Clearly, the tumor cells and their microenvironment may have an influence on the action of recruited MSCs [59]. Taken together, both postulations seem concomitantly true and therefore, it is very hard to make a prediction to the effects of MSCs on the cancerous process [60,61]. tumor-promoting or a tumor-limiting effects depending on the experimental circumstances [13].…”

“…To author knowledge, MSCs have shown tumor suppressive effects in induced murine HCC that were linked to down regulation of Wnt signaling target genes [60,62]. There are several suggested mechanisms lying behind this action.…”

LY3214996 relieves acquired resistance to sorafenib in hepatocellular carcinoma cells

“…Despite encouraging progress was acquired, treatments for patients with advanced HCC are still very limited owing to acquired sorafenib resistance, and further development of new treatment options is necessary. In addition, the low response rate of sorafenib is a worrying phenomenon and epithelial-mesenchymal transition (EMT), Ras/Raf/MAPK, PI3K/Akt, JAK/STAT pathways, hypoxia, and many other mechanisms were considered to be the main obstacles that led to the failure of sorafenib in HCC patients [9][10][11].…”