Cancer Stem Cells Protect Non‐Stem Cells From Anoikis: Bystander Effects

Abstract

Cancer stem cells (CSCs) are capable of initiation and metastasis of tumors. Therefore, understanding the biology of CSCs and the interaction between CSCs and their counterpart non-stem cells is crucial for developing a novel cancer therapy. We used CSC-like and non-stem breast cancer MDA-MB-231 and MDA-MB-453 cells to investigate mammosphere formation. We investigated the role of the epithelial cadherin (E-cadherin)-extracellular signal-regulated kinase (Erk) axis in anoikis. Data from E-cadherin small hairpin RNA assay and mitogen-activated protein kinase kinase (MEK) inhibitor study show that activation of Erk, but not modulation of E-cadherin level, may play an important role in anoikis resistance. Next, the two cell subtypes were mixed and the interaction between them during mammosphere culture and xenograft tumor formation was investigated. Unlike CSC-like cells, increased secretion of interleukin-6 (IL-6) and growth-related oncogene (Gro) chemokines was detected during mammosphere culture in non-stem cells. Similar results were observed in mixed cells. Interestingly, CSC-like cells protected non-stem cells from anoikis and promoted tumor growth. Our results suggest bystander effects between CSC-like cells and non-stem cells. J. Cell. Biochem. 117: 2289-2301, 2016. © 2016 Wiley Periodicals, Inc.

Isolation of spheroid-forming single cells from gastric cancer cell lines: enrichment of cancer stem-like cells

“…The above results suggested that the derived spheroids are composed of mixed cell populations, including non-CSCs, as previously reported [25]. To test this hypothesis, the percentages of dead and apoptotic cells in both TS#2 and SS#2 spheroids were measured using a live/dead cell viability assay kit and an annexin V-FITC apoptosis detection kit, respectively, according to the manufacturers instructions.…”

“…Additionally, these methods may result in the formation of spheroids containing many cells that are not CSCs. A recent report showed that CSC-like cells protect non-CSCs from anoikis and also promote tumor growth [25]. As spheroid bodies themselves display marked cellular heterogeneity, experiments using spheroids should be interpreted as studies of mixed cell populations, not as purified CSCs [29].…”

TDO2 Overexpression Is Associated with Cancer Stem Cells and Poor Prognosis in Esophageal Squamous Cell Carcinoma

“…A previous report showed that TDO2 facilitates anoikis resistance in triple-negative breast cancer [18], and another study indicated that resistance to anoikis was related to CSC-like cells [30]. Thus, we hypothesized that TDO2 expression may be related to CSC marker expression in ESCC.…”

CD166high Uveal Melanoma Cells Represent a Subpopulation With Enhanced Migratory Capacity

“…27 CSCs in several cancers including breast have been shown to be resistant to anoikis, form spheres in nonadherent culture and have enhanced tumor growth capacity. 28 UM cells surviving anoikis showed an increased expression of several markers previously associated with neural crest development and stem cells: CD271, Nestin, and CD166. CD271 has been shown to mark the CSC population in skin melanoma.…”