CD133+ cells with cancer stem cell characteristics associates with vasculogenic mimicry in triple-negative breast cancer

Abstract

Vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks. In the study we demonstrated that CD133 expression was the highest in triple-negative (TN) breast cancer specimens. Importantly, VM showed statistical correlation with CD133(+) expression. The presence of the close relationship between VM and CD133(+) expression might be central for TN tumor relapse and progression. The TN breast cancer cell line, MDA-MB-231 cells developed a range of colony morphologies paralleling the holoclone, meroclone and paraclone morphologies produced by normal keratinocytes and other epithelial cancer cell lines when plated at clonal densities. Holoclone cells were capable of forming more colonies on soft agar than meroclone cells and paraclone cells, suggesting that holoclone cells had higher self-renew potential and might harbors cancer stem cells (CSCs) subpopulation. Strikingly, it was holoclone that displayed CD133(+) phenotype and formed VM. In addition, holoclone acquired endothelial cell marker vascular endothelial-cadherin expression and upregulated VM mediators matrix metalloproteinase (MMP)-2 and MMP-9 expression. The subpopulation with holoclone morphology, CD133(+) phenotype and CSCs characteristics might have the capacity of transdifferentiation and contributed to VM in TN breast cancer. The related molecular pathways may be used as novel therapeutic targets for the inhibition of angiogenesis and metastasis in TN breast carcinoma.

Featured Article: Downregulation of transgelin blocks interleukin-8 utilization and suppresses vasculogenic mimicry in breast cancer cells

“…29 In addition, IL-8 signaling is known to affect MMP-2, which has been implicated ....................................................................................................................... in VM. 9,18,19 Moreover, the highly invasive MDA-MB-231 cells are known to secrete IL-8. 30,31 We determined the levels of IL-8 secreted by cells grown as monolayers and on Matrigel, and assessed the impact of transgelin on this process.…”

“…VM is usually observed in highgrade invasive tumors, is associated with poor prognosis, and might be partly responsible for resistance to antiangiogenic drugs. [7][8][9] Indeed, a number of studies revealed that angiogenesis inhibitors did not significantly affect VM, thus underscoring the need for improved antivascular therapies that specifically target VM. 6,10,11 Transgelin (also known as SM22a and TAGLN) is an early marker of smooth muscle cell differentiation and is an actin-binding protein that affects cytoskeletal dynamics by stabilizing actin filaments.…”

Implications of Different Cancer Stem Cell Phenotypes in Breast Cancer

“…Actually, in BRCA1-associated breast cancer cell lines, CD133 + sorted cells were shown to have CSC properties, including a greater colony-forming efficiency, higher proliferative output and greater capability to form tumors in NOD/SCID mice (67). Moreover, CD133 was also proved to be suitable in the identification of CSCs in triplenegative breast cancers through several in vitro (68,69) and in vivo studies (70). In addition, the recent use of CD133 to detect circulating tumor cells in patients with triple-negative breast cancer (71,72) has increased the attention on this marker, emphasizing its role in prognosis in this breast cancer subtype.…”

Analysis of multiple markers for cancer stem-like cells in human thyroid carcinoma cell lines

“…- [3], aldehyde dehydrogenase (ALDH) 1 activity [7], and CD133 [8] for breast CSCs; CD133 [5] and CD44 + /CD24 + [9] for colon CSCs. However, their association and/or combination have not been fully investigated.…”