Spontaneous Cell Detachment and Reattachment in Cancer Cell Lines : An In Vitro Model of Metastasis and Malignancy
Vargas-Accarino, Elena (Hospital Universitari Vall d'Hebron)
Herrera-Montávez, Carlos (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Ramón y Cajal, Santiago (Centro de Investigación Biomédica en Red de Cáncer)
Aasen, Trond (Universitat Autònoma de Barcelona)

Data:	2021
Resum:	There is an unmet need for simplified in vitro models of malignancy and metastasis that facilitate fast, affordable and scalable gene and compound analysis. "Adherent" cancer cell lines frequently release "free-floating" cells into suspension that are viable and can reattach. This, in a simplistic way, mimics the metastatic process. We compared the gene expression profiles of naturally co-existing populations of floating and adherent cells in SW620 (colon), C33a (cervix) and HeLa (cervix) cancer cells. We found that 1227, 1367 and 1333 genes were at least 2-fold differentially expressed in the respective cell lines, of which 122 were shared among the three cell lines. As proof of principle, we focused on the anti-metastatic gene NM23-H1, which was downregulated both at the RNA and protein level in the floating cell populations of all three cell lines. Knockdown of NM23-H1 significantly increased the number of floating (and viable) cells, whereas overexpression of NM23-H1 significantly reduced the proportion of floating cells. Other potential regulators of these cellular states were identified through pathway analysis, including hypoxia, mTOR (mechanistic target of rapamycin), cell adhesion and cell polarity signal transduction pathways. Hypoxia, a condition linked to malignancy and metastasis, reduced NM23-H1 expression and significantly increased the number of free-floating cells. Inhibition of mTOR or Rho-associated protein kinase (ROCK) significantly increased cell death specifically in the floating and not the adherent cell population In conclusion, our study suggests that dynamic subpopulations of free-floating and adherent cells is a useful model to screen and identify genes, drugs and pathways that regulate the process of cancer metastasis, such as cell detachment and anoikis.
Ajuts:	Instituto de Salud Carlos III PI16/007 Ministerio de Economía y Competitividad CPII16/00042
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Metastasis models ; Floating cells ; Suspension cells ; Anoikis ; NM23 ; Mtor ; Cell detachment ; Cell reattachment
Publicat a:	International journal of molecular sciences, Vol. 22 (may 2021) , ISSN 1422-0067

DOI: 10.3390/ijms22094929
PMID: 34066490

19 p, 4.2 MB

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