Bidirectional and Opposite Effects of Naïve Mesenchymal Stem Cells Ontumor Growth and Progression

Rahmatizadeh, Faramarz; Aziz, Shiva Gholizadeh‐Ghaleh; Khodadadi, Khodadad; Ataei, Maryam Lale; Ebrahimie, Esmaeil; Rad, Jafar Soleimani; Pashaiasl, Maryam

doi:10.15171/apb.2019.063

Cited by 15 publications

(13 citation statements)

References 232 publications

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“…The TME, also known as the tumor stroma, consists of connective tissue and a variety of non-cancer cell types. Immune cells such as macrophages, cancer-associated fibroblasts (CAFs), and lymphocytes residing in the stroma have been shown to exhibit bidirectional effects on tumor progression (14)(15)(16). The tumor stroma is associated with prognosis in a variety of cancer types (17)(18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Increased RAB31 Expression in Cancer-Associated Fibroblasts Promotes Colon Cancer Progression Through HGF-MET Signaling

et al. 2020

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RAB family proteins participate in the dynamic regulation of cellular membrane compartments and are dysregulated in a variety of tumor types, which may alter the biological properties of cancer cells such as proliferation, migration, and invasion. In our previous study, we found that Ras-related protein Rab-31 (RAB31) expression was increased in late-stage colorectal cancer (CRC). The role of RAB31 has never been investigated in CRC. In this study, we found that expression of RAB31 in the tumor stroma but not cancer cells of colon cancer predicted poor survival. RAB31 can be detected in primary cancer-associated fibroblasts (CAFs) and paired normal fibroblasts. Conditioned medium (CM) from RAB31 overexpressing CAFs significantly promoted migration of colon cancer cell lines in vitro and in vivo. This process may be mediated by paracrine action of hepatocyte growth factor (HGF), which was increased in the CM of RAB31-overexpressing CAFs. Blockade of HGF/MET signaling by drug inhibition, knockdown of mesenchymal to epithelial transition factor (MET) in RKO, or antibody neutralization of HGF abolished migration of RKO cells mediated by RAB31 expression in CAFs. We propose that in colon cancer, increased RAB31 expression in CAFs may contribute to tumor progression by regulating the secretion of HGF in the tumor stroma.

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Section: Introductionmentioning

confidence: 99%

Increased RAB31 Expression in Cancer-Associated Fibroblasts Promotes Colon Cancer Progression Through HGF-MET Signaling

et al. 2020

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“…Despite the potential benefits of using MSC as a cell delivery system, studies have reported the supportive role of MSC in the progression of tumor density and metastasis, while others have shown antitumor effects both in vitro and in different models of cancer ( Devarasetty et al, 2017 ; Liang et al, 2020 ; Xia et al, 2020 ). The conflicting data in the literature may hamper the establishment of cell therapies for cancer based on non-modified MSC since the therapeutic safety of such approach might be jeopardized ( Rahmatizadeh et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…The majority of the studies evaluating the effect of naïve MSC on tumor development employ MSC from the BM, the UCM, and the AT ( Rahmatizadeh et al, 2019 ; Liang et al, 2020 ; Xia et al, 2020 ). When analyzing the outcome from these studies, it seems to be a conspicuous pattern of tumorigenicity, with BM MSC being more pro-tumorigenic and UCM MSC being more tumor suppressive.…”

Section: Discussionmentioning

confidence: 99%

“…When evaluating the role of naïve MSC in tumor progression/suppression, the majority of studies employ MSC isolated from the BM, the UCM, and the adipose tissue (AT) ( Rahmatizadeh et al, 2019 ; Liang et al, 2020 ; Xia et al, 2020 ). Considering that MSC isolated from different tissue sources express different surface markers ( Hass et al, 2011 ; Elahi et al, 2016 ), and may differ in what concerns differentiation potential ( Rebelatto et al, 2008 ), the outcome from these studies may be dependent on the isolation source of MSC.…”

Section: Introductionmentioning

confidence: 99%

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Conditioned Medium From Azurin-Expressing Human Mesenchymal Stromal Cells Demonstrates Antitumor Activity Against Breast and Lung Cancer Cell Lines

Silva

Monteiro

Fialho

et al. 2020

Front. Cell Dev. Biol.

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Recently, cell-based therapies have been explored as a strategy to enhance the specificity of anticancer therapeutic agents. In this perspective, human mesenchymal stromal cells (MSC) hold a promising future as cell delivery systems for anticancer proteins due to their unique biological features. In this study, we engineered human MSC to secrete a human codon-optimized version of azurin (hazu), a bacterial protein that has demonstrated anticancer activity toward different cancer models both in vitro and in vivo . To this end, microporation was used to deliver plasmid DNA encoding azurin into MSC derived from bone marrow (BM) and umbilical cord matrix (UCM), leading to expression and secretion of hazu to the conditioned medium (CM). Engineered hazu-MSC were shown to preserve tumor tropism toward breast (MCF-7) and lung (A549) cancer cell lines, comparable to non-modified MSC. Azurin was detected in the CM of transfected MSC and, upon treatment with hazu-MSC-CM, we observed a decrease in cancer cell proliferation, migration, and invasion, and an increase in cell death for both cancer cell lines. Moreover, expression of azurin caused no changes in MSC expression profile of cytokines relevant in the context of cancer progression, thus suggesting that the antitumoral effects induced by hazu-MSC secretome might be due to the presence of azurin independently. In conclusion, data shown herein indicate that MSC-produced azurin in a CM configuration elicits an anticancer effect.

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“…The role of MSCs in tumors is still controversial, but their supportive role in tumor progression is dominant. 177,178 The results of two studies in EC also show that MSCs promote progression of tumor in vivo, 179,180 which is a promising therapeutic direction, but the research on its specific mechanism and related effects need to be further studied.…”

Section: Tumor Stromal Cells Are Imperative Supporters For Tmementioning

confidence: 99%

<p>Esophageal Microenvironment: From Precursor Microenvironment to Premetastatic Niche</p>

Han¹,

Cao²,

Huang³

et al. 2020

CMAR

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Esophageal cancer (EC) is the sixth most deadly cancer, and its incidence is still increasing year by year. Although the researches on the molecular mechanisms of EC have been widely carried out and incremental progress has been made, its overall survival rate is still low. There is cumulative evidence showing that the esophageal microenvironment plays a vital role in the development of EC. In precancerous lesions of the esophagus, high-risk environmental factors can promote the development of precancerous lesions by inducing the production of inflammatory factors and the recruitment of immune cells. In the tumor microenvironment, tumor-promoting cells can inhibit anti-tumor immunity and promote tumor progression through a variety of pathways, such as bone marrow-derived suppressor cells (MDSCs), tumor-associated fibroblasts (CAFs), and regulatory T cells (Tregs). The formation of extracellular hypoxia and acidic microenvironment and the change of extracellular matrix stiffness are also important factors affecting tumor progression and metastasis. Simultaneously, primary tumor-derived cytokines and bone marrow-derived immune cells can also promote the formation of pre-metastasis niche of EC lymph nodes, which are beneficial to EC lymph node metastasis. Further research on the specific mechanism of these processes in the occurrence, development, and metastasis of each EC subtype will support us to grasp the overall pre-cancerous prevention, targeted treatment, and metastatic assessment of EC.

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Bidirectional and Opposite Effects of Naïve Mesenchymal Stem Cells Ontumor Growth and Progression

Cited by 15 publications

References 232 publications

Increased RAB31 Expression in Cancer-Associated Fibroblasts Promotes Colon Cancer Progression Through HGF-MET Signaling

Increased RAB31 Expression in Cancer-Associated Fibroblasts Promotes Colon Cancer Progression Through HGF-MET Signaling

Conditioned Medium From Azurin-Expressing Human Mesenchymal Stromal Cells Demonstrates Antitumor Activity Against Breast and Lung Cancer Cell Lines

<p>Esophageal Microenvironment: From Precursor Microenvironment to Premetastatic Niche</p>

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