Adipose-Derived Mesenchymal Stem Cells Promote Growth and Migration of Lung Adenocarcinoma Cancer Cells
Introduction: Mesenchymal stem cells (MSCs) have been used in cancer therapy as vehicles to deliver therapeutic materials such as drugs, apoptosis inducers and cytokines due to their ability to migrate and home at the tumour site. Furthermore, MSCs have b
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Adipose-Derived Mesenchymal Stem Cells Promote Growth and Migration of Lung Adenocarcinoma Cancer Cells Norashikin Zakaria and Badrul Hisham Yahaya Abstract
Introduction: Mesenchymal stem cells (MSCs) have been used in cancer therapy as vehicles to deliver therapeutic materials such as drugs, apoptosis inducers and cytokines due to their ability to migrate and home at the tumour site. Furthermore, MSCs have been genetically engineered to produce anticancer molecules such as TRAIL that can induce apoptosis of cancer cells. However, MSCs’ presence in the tumour microenvironment has shown to be involved in promoting tumour growth and progression. Therefore, the roles of MSCs either promoting or suppressing tumorigenesis need to be investigated. Methods: Human adipose-derived MSCs (Ad-MSCs) and A549 cells are co-cultured together in indirect co-culture system using Transwell insert. Following co-culture, both cells were analysed in terms of growth rate, migration ability, apoptosis and gene expression for genes involved in migration and stemness characteristics. Results: The result shows that Ad-MSCs promoted the growth of A549 cells when indirectly co-cultured for 48 and 72 h. Furthermore, Ad-MSCs significantly enhanced the migration rate of A549 cells. The increased in migration rate was in N. Zakaria and B. H. Yahaya (*) Regenerative Medicine Cluster, Advanced Medical & Dental Institute (AMDI), Universiti Sains Malaysia, Kepala Batas, Penang, Malaysia e-mail: [email protected]; [email protected]
parallel with the significant increase of MMP9. There are no significant changes observed in the expression of TWIST2, CDH2 and CDH1, genes involved in the epithelial-to-mesenchymal transition (EMT). Ad-MSCs also protect A549 cancer cells from undergoing apoptosis and increase the survival of cancer cells. Conclusion: Secretion of soluble factors from Ad-MSCs has been shown to promote the growth and metastatic characteristics of A549 cancer cells. Therefore, the use of Ad-MSCs in cancer therapy needs to be carefully evaluated in the long-term aspect. Keyword
Adipose-derived stem cells · Co-culture · Lung cancer · MSCs
Abbreviation AD AdMSCs BMMSCs cDNA CSCs EMT LCC MSCs NSCLC
Adenocarcinoma Human adipose-derived mesenchymal stem cells Bone marrow-derived mesenchymal stem cells Complementary DNA Cancer stem cells Epithelial-to-mesenchymal transition Large-cell carcinoma Mesenchymal stem cells Non-small cell lung carcinoma
N. Zakaria and B. H. Yahaya
SCC TME TRAIL
1
Squamous cell carcinoma Tumour microenvironment TNF-related apoptosis-inducing ligand
Introduction
Lung cancer remains as the world’s most diagnosed cancer which accounts for 11.6% of the total cancer cases and the leading cause of world’s cancer-related mortality (Bray et al. 2018). The majority of lung cancer cases are non-small cell lung carcinoma (NSCLC) (85%) which is further sub-divided into adenocarcinoma (AD), squamous cell carcinoma (SCC) and largecell carcinoma (LCC) that comprise about 50%, 40% and < 10% of NSCLC, respectively (Travis et
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