TGF-β1 stimulates epithelial–mesenchymal transition and cancer-associated myoepithelial cell during the progression from in situ to invasive breast cancer

Wang, Li; Xu, Cong; Liu, Xia; Yang, Yang; Cao, Lu; Xiang, Guomin; Liu, Fang; Wang, Shuling; Liu, Jing; Meng, Qingxiang; Jiao, Jiao; Niu, Yun

doi:10.1186/s12935-019-1068-7

Cited by 15 publications

(11 citation statements)

References 30 publications

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“…In culture and in vivo studies identified that myoepithelial cell expression of integrin β6 enhanced breast tumour cell invasion through TGFβ-mediated upregulation of MMP9 36 . In support of our previous work, others have demonstrated, using in vitro studies, that tumour-associated myoepithelial cells secrete TGFβ to promote the invasive progression of DCIS cells due to enhancing epithelial-to-mesenchymal transition and basal-like phenotypes through activation of the TGFβ/SMAD signalling pathway 37 , 38 . However, the mechanisms inducing such alterations to DCIS myoepithelial cells are largely unknown.…”

Section: Introductionsupporting

confidence: 76%

Mechanostimulation of breast myoepithelial cells induces functional changes associated with DCIS progression to invasion

et al. 2022

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Women with ductal carcinoma in situ (DCIS) have an increased risk of progression to invasive breast cancer. Although not all women with DCIS will progress to invasion, all are treated as such, emphasising the need to identify prognostic biomarkers. We have previously shown that altered myoepithelial cells in DCIS predict disease progression and recurrence. By analysing DCIS duct size in sections of human breast tumour samples, we identified an associated upregulation of integrin β6 and an increase in periductal fibronectin deposition with increased DCIS duct size that associated with the progression of DCIS to invasion. Our modelling of the mechanical stretching myoepithelial cells undergo during DCIS progression confirmed the upregulation of integrin β6 and fibronectin expression in isolated primary and cell line models of normal myoepithelial cells. Our studies reveal that this mechanostimulated DCIS myoepithelial cell phenotype enhances invasion in a TGFβ-mediated upregulation of MMP13. Immunohistochemical analysis identified that MMP13 was specifically upregulated in DCIS, and it was associated with progression to invasion. These findings implicate tissue mechanics in altering the myoepithelial cell phenotype in DCIS, and that these alterations may be used to stratify DCIS patients into low and high risk for invasive progression.

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Section: Introductionsupporting

confidence: 76%

Mechanostimulation of breast myoepithelial cells induces functional changes associated with DCIS progression to invasion

et al. 2022

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“…These conflicting results might be due to the observation that MCF7 differentially expresses TGF-β receptor II depending on the cell passage number and the downregulation of Sp1 [44,45]. Notably, consistent with our findings, many studies have reported that TGF-β1 does induce EMT and migration in MCF7 [46][47][48].…”

Section: Tgf-β1 Pathway Mediates the Recruitment Of Less Aggressive C...supporting

confidence: 59%

<strong></strong>Interclonal Mutually Beneficial Cooperation Mediated by TGF-β1 Enhances Invasion of Breast Cancer Cells

Carneiro¹,

Hapeman²,

Nedelcu³

2022

Preprint

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Intratumour heterogeneity is often associated with poor response to treatment and bad prognosis. In addition to genetic and epigenetic sources, phenotypic heterogeneity can also reflect plastic responses to signals from other cells. The latter can be mediated by various cell-cell interactions, from antagonistic (i.e., competition) to commensalistic or cooperative (mutually beneficial or altruistic). Positive exchanges can increase the fitness of clones and contribute to tumour growth, resistance to drugs and metastasis. Consequently, understanding the pathways involved in such interactions is of great significance for cancer treatment. This study used two breast cancer cell lines with different aggressiveness levels and very different secretome profiles (i.e., MDA-MB-231 and MCF7) to address the nature and mechanistic basis of interclonal crosstalk through paracrine signalling involving soluble factors during the early stages of metastasis. Our data show that MDA-MB-231 is able to recruit MCF7, through TGFβ1-mediated paracrine signalling, into expressing mesenchymal features and increased migration. On the other hand, MCF7 has no effect on the migration of MDA, suggesting a passive/commensalistic interaction. However, we found that the invasive potentials of both lines are enhanced when they are co-cultured, indicating that the two lines act synergistically and that such interclonal interactions can be mutually beneficial in vivo. Taking into account the negative impact that metastasis has on cancer prognosis and the lack of therapies to directly affect this process, interfering with the specific cooperative behaviours that tumour cells engage in during tumour progression should provide an additional strategy to increase patient survival.

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“…Analysis of humoral factors mediating the interrelation between tumor cells and fibroblasts within the tumor microenvironment has been reported for several carcinomas such as breast cancer 18 , prostate cancer 19 , and lung cancer. There have been many studies on the relationship with normal cells in epithelial tumors, in cancer-related fibroblasts where fibroblasts acquire the properties of mesenchymal cells 20 – 22 . In addition, the number of studies described the effects of humoral factors on immune cells.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the signal cross talk via CCL26 in the tumor microenvironment in osteosarcoma

Kawano

Iwasaki

Itonaga

et al. 2021

Sci Rep

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Interaction with surrounding healthy cells plays a major role in the growth and metastasis of osteosarcoma. In this study, we hypothesized that humoral factors, which do not require direct contact with cells, are involved in the interaction between osteosarcoma and the surrounding cells. We identified the humoral factor involved in the association between tumor cells and surrounding normal cells using a co-culture model and investigated the significance of our findings. When human osteosarcoma cells (MG63) and human mesenchymal stem cells (hMSCs) were co-cultured and comprehensively analyzed for changes in each culture group, we found that the expression of chemokine (CC motif) ligand 26 (CCL26) was significantly enhanced. We also analyzed the changes in cell proliferation in co-culture, enhanced interaction with administration of recombinant CCL26 (rCCL26), reduced interaction with administration of anti-CCL26 antibodies, changes in invasive and metastatic abilities. CCL26 levels, motility, and invasive capability increased in the co-culture group and the group with added rCCL26, compared to the corresponding values in the MG63 single culture group. In the group with added CCL26 neutralizing antibodies, CCL26 level decreased in both the single and co-culture groups, and motility and invasive ability were also reduced. In a nude mice lung metastasis model, the number of lung metastases increased in the co-culture group and the group with added rCCL26, whereas the number of tumors were suppressed in the group with added neutralizing antibodies compared to those in the MG63 alone. This study identified a possible mechanism by which osteosarcoma cells altered the properties of normal cells to favorably change the microenvironment proximal to tumors and to promote distant metastasis.

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TGF-β1 stimulates epithelial–mesenchymal transition and cancer-associated myoepithelial cell during the progression from in situ to invasive breast cancer

Cited by 15 publications

References 30 publications

Mechanostimulation of breast myoepithelial cells induces functional changes associated with DCIS progression to invasion

Mechanostimulation of breast myoepithelial cells induces functional changes associated with DCIS progression to invasion

<strong></strong>Interclonal Mutually Beneficial Cooperation Mediated by TGF-β1 Enhances Invasion of Breast Cancer Cells

Analysis of the signal cross talk via CCL26 in the tumor microenvironment in osteosarcoma

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