scholarly journals Mesenchymal stem cells carry and transport clusters of cancer cells

2021 ◽  
Author(s):  
Jana Zarubova ◽  
Mohammad Mahdi Hasani-Sadrabadi ◽  
Sam CP Norris ◽  
Andrea M Kasko ◽  
Song Li

AbstractCell clusters that collectively migrate from primary tumors appear to be far more potent in forming distant metastases than single cancer cells. A better understanding of collective cell migration phenomenon and the involvement of different cell types during this process is needed. Here, we utilize a micropatterned surface composed of a thousand of low-adhesive microwells to screen motility of spheroids containing different cell types by analyzing their ability to move from the bottom to the top of the microwells. Mesenchymal stem cells (MSCs) spheroid migration was efficient in contrast to cancer cell only spheroids. In spheroids with both cell types mixed together, MSCs were able to carry the low-motile cancer cells during migration. As the percentage of MSCs increased in the spheroids, more migrating spheroids were detected. Extracellular vesicles secreted by MSCs also contributed to the pro-migratory effect exerted by MSCs. However, the transport of cancer cells was more efficient when MSCs were physically present in the cluster. Similar results were obtained when cell clusters were encapsulated within a micropatterned hydrogel, where collective migration was guided by micropatterned matrix stiffness. These results suggest that stromal cells facilitate the migration of cancer cell clusters, which is contrary to the general belief that malignant cells metastasize independently.SignificanceDuring metastasis, tumor cells may migrate as a cluster, which exhibit higher metastatic capacity compared to single cells. However, whether and how non-cancer cells contained in tumor cluster regulate it’s migration is not clear. Here, we utilize two unique approaches to study collective tumor cell migration in vitro: first, in low-adhesive microwells and second, in micropatterned hydrogels to analyze migration in 3D microenvironment. Our results indicate that MSCs in tumor cell clusters could play an important role in the dissemination of cancer cells by actively transporting low-motile cancer cells. In addition, MSC-released paracrine factors also increase the motility of tumor cells. These findings reveal a new mechanism of cancer cell migration and may lead to new approaches to suppress metastases.

2021 ◽  
Vol 22 ◽  
Author(s):  
Soheila Montazersaheb ◽  
Ezzatollah Fathi ◽  
Ayoub Mamandi ◽  
Raheleh Farahzadi ◽  
Hamid Reza Heidari

: Tumors are made up of different types of cancer cells that contribute to tumor heterogeneity. Among these cells, cancer stem cells (CSCs) have a significant role in the onset of cancer and development. Like other stem cells, CSCs are characterized by the capacity for differentiation and self-renewal. A specific population of CSCs is constituted by mesenchymal stem cells (MSCs) that differentiate into mesoderm-specific cells. The pro-or anti-tumorigenic potential of MSCs on the proliferation and development of tumor cells has been reported as contradictory results. Also, tumor progression is specified by the corresponding tumor cells like the tumor microenvironment. The tumor microenvironment consists of a network of reciprocal cell types such as endothelial cells, immune cells, MSCs, and fibroblasts as well as growth factors, chemokines, and cytokines. In this review, recent findings related to the tumor microenvironment and associated cell populations, homing of MSCs to tumor sites, and interaction of MSCs with tumor cells will be discussed.


Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4350
Author(s):  
Jessica Castro ◽  
Giusy Tornillo ◽  
Gerardo Ceada ◽  
Beatriz Ramos-Neble ◽  
Marlon Bravo ◽  
...  

Despite the significant advances in cancer research made in recent years, this disease remains one of the leading causes of death worldwide. In part, this is due to the fact that after therapy, a subpopulation of self-renewing tumor cells can survive and promote cancer relapse, resistance to therapies and metastasis. Targeting these cancer stem cells (CSCs) is therefore essential to improve the clinical outcome of cancer patients. In this sense, multi-targeted drugs may be promising agents targeting CSC-associated multifocal effects. We have previously constructed different human pancreatic ribonuclease (RNase) variants that are cytotoxic for tumor cells due to a non-classical nuclear localization signal introduced in their sequence. These cytotoxic RNases affect the expression of multiple genes involved in deregulated metabolic and signaling pathways in cancer cells and are highly cytotoxic for multidrug-resistant tumor cell lines. Here, we show that these cytotoxic nuclear-directed RNases are highly selective for tumor cell lines grown in 3D, inhibit CSCs’ development and diminish the self-renewal capacity of the CSCs population. Moreover, these human RNase variants reduce the migration and invasiveness of highly invasive breast cancer cells and downregulate N-cadherin expression.


2019 ◽  
Vol 9 (7) ◽  
pp. 904-913
Author(s):  
Bing Yan ◽  
Ruining Liang ◽  
Meng Ji ◽  
Qi-Qige Wuyun ◽  
Weijun Guan ◽  
...  

Of all the significant researches that have taken place in isolation, culture and characterization of mesenchymal stem cells (MSCs), the field of kidney-derived mesenchymal stem cells (KMSCs) in Tibetan mastiff is still a blank. Therefore, the purpose of this study is to isolate, culture and characterize the Tibetan mastiff KMSCs. The KMSCs were successfully isolated from one-day year old Tibetan mastiff kidney, cultured for 16 passages and distinguished by two methods: immunofluorescence staining and RT-PCR. The Tibetan mastiff KMSCs expressed specific surface marker genes (VIM, CD44, FN1, CD90, CD109, CD73, FN1) and kidney marker gene PAX2. The proliferation ability of Tibetan mastiff KMSCs was measured through cell count and clonality. Furthermore, cells differentiated into different cell types (hepatocellular cells, osteogenic cells, adipogenic cells and chondrogenic cells) under special induced medium, and the marker genes of induced cells were identified with Immunofluorescence staining and RT-PCR. All of these results indicated that the Tibetan mastiff KMSCs were obtained successfully, which possessed certain characteristics of multipotent stem cells. Therefore, MSCs in Tibetan mastiff kidney hold potential for clinical applications for regenerative therapy and their further studies are waiting to be required to investigate their functions.


2021 ◽  
Vol 9 (A) ◽  
pp. 748-752
Author(s):  
Sahar Hassan Ahmed ◽  
Abeer Mostafa ◽  
Amany Abou-Elalla

AIM: Cancer breast is one of the most common cancer in women leading to death; that is why we are in urgent need to develop new modalities of treatment. Mesenchymal stem cells (MSCs) have an anti-inflammatory effect due to capability to regenerate the damaged tissues. METHODS: MCF7 breast cancer cells were divided into two groups; group 1: untreated cancer cells, group 2: cancer cell cocultured with MSCs; after 24 incubation the cells from the two groups were collected to assess cell proliferation, Interleukin-6 (IL-6) levels and genes expression of Nuclear factor-kappa B (NF-KB), FOXO, and LncRNA AF085935. RESULTS: Statistically significant decrease in cancer cell proliferation and all other studied parameters in cancer cells after coculture with MSCs. CONCLUSION: Breast carcinoma once initiated; it runs in a vicious circle due to stimulation of FOXO/LncRNA AF085935 axis by the inflammatory mediators released from cancer environment. FOXO/LncRNA AF085935 induces cancer proliferation and survival; furthermore, FOXO once induced, it produces further induction of inflammatory cytokines IL-6 and NF-KB and so on, MSCs due to its anti-inflammatory role could break this circle and thus inhibit cancer cell proliferation.


2013 ◽  
Vol 114 (5) ◽  
pp. 1135-1144 ◽  
Author(s):  
Cinzia Borghese ◽  
Lara Cattaruzza ◽  
Eliana Pivetta ◽  
Nicola Normanno ◽  
Antonella De Luca ◽  
...  

Nanoscale ◽  
2017 ◽  
Vol 9 (28) ◽  
pp. 9848-9858 ◽  
Author(s):  
Maria del Mar Encabo-Berzosa ◽  
Maria Sancho-Albero ◽  
Alejandra Crespo ◽  
Vanesa Andreu ◽  
Victor Sebastian ◽  
...  

Mesenchymal stem cells (MSCs) not only can be differentiated into different cell types but also have tropism towards injured or inflamed tissues serving as repair cells.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22097-e22097
Author(s):  
T. Kaiser ◽  
G. Klein ◽  
E. Solomayer ◽  
D. Wallwiener ◽  
T. Fehm

e22097 Background: Bone is one of the most favored sites for metastasis of breast cancer cells (BrCa) resulting in the formation of osteolytic and/or osteoblastic lesions. There is increasing evidence that the bone marrow (BM) microenvironment plays a pivotal role in modulating tumor cell homing to the bone, metastasis and progression. However, the molecular crosstalk between BrCa cells and the cellular and extracellular components of the bone marrow leading to osteotropism still remains a poorly characterized step in the metastatic process. Methods: Cell adhesion and migration assays using the invasive MDA-MB-231 and the noninvasive MCF7 BrCa cell lines were performed to investigate the impact of BM components on cellular functions of tumor cells. Results: Cell-matrix adhesion assays showed a strong and concentration-dependent attachment of BrCa cells to several extracellular matrix components present in the human bone marrow such as fibronectin, different laminin isoforms, collagens type I and IV or tenascin-C. Moreover, the BrCa cells attached avidly to the BM-derived primary osteoblasts, whereas the binding to stromal cells was significantly weaker. Notably, cell-cell adhesion experiments with primary osteoclasts revealed an anti-adhesive effect on tumor cell binding leading to no attachment activity of BrCa cells with the cell surface of primary osteoclasts. The influence of cellular components of the BM on tumor cell migration was analyzed by cell migration assays using conditioned media of osteoblasts, osteoclasts and stromal cells or a modified Transwell chamber technique. The migration assays with invasive MDA-MB-231 cells clearly showed that osteoblasts, but not osteoclasts or stromal cells released factors which led to a faster wound closure, suggesting an enhanced migratory ability of the metastatic tumor cells, whereas the migration of nonmetastatic MCF7 cells was unaffected. Conclusions: These data indicate that the crosstalk with osteoblasts affects both the adhesive and the migratory ability of BrCa cells favoring the bone colonization process. Furthermore, the presented experimental conditions may provide useful tools to study effects of antiresorptive drugs like bisphosphonates to improve therapeutic strategies for treatment metastatic bone disease. No significant financial relationships to disclose.


2011 ◽  
Vol 308 (1) ◽  
pp. 91-99 ◽  
Author(s):  
Jennifer L. Halpern ◽  
Amy Kilbarger ◽  
Conor C. Lynch

Sign in / Sign up

Export Citation Format

Share Document