Epithelial-to-mesenchymal transition (EMT) induced by inflammatory priming elicits mesenchymal stromal cell-like immune-modulatory properties in cancer cells

Ricciardi, Mario; Zanotto, Marco; Malpeli, Giorgio; Bassi, Giulio; Perbellini, Omar; Chilosi, Marco; Bifari, Francesco; Krampera, Mauro

doi:10.1038/bjc.2015.29

Cited by 145 publications

(116 citation statements)

References 31 publications

Supporting

Mentioning

111

Contrasting

Order By: Relevance

“…While the EMT mechanism was enhanced by TALs-CM-pLNs via regulating the expression of E-cadherin and vimentin by MCF-7 cells. Our findings are supported by recent study showed that EMT was induced by supernatant of mixed lymphocytes or inflammatory cytokines in different carcinoma cell lines including breast carcinoma cell line MCF-7 [33]. The EMT phenotype induced by inflammatory cytokines gave carcinoma cells-specific immune escape properties that facilitate metastasis [33] and the co-culture model of lung carcinoma cells and immune cells (A549 and THP1) stimulate EMT in carcinoma cells; a mechanism that was modulated via pro-inflammatory cytokines secreted by immune cells and is inhibited by tectorigenin [34].…”

Section: Discussionsupporting

confidence: 91%

Secretome of tumor-associated leukocytes augment epithelial-mesenchymal transition in positive lymph node breast cancer patients via activation of EGFR/Tyr845 and NF-κB/p65 signaling pathway

et al. 2016

View full text Add to dashboard Cite

Epithelial-mesenchymal transition (EMT) is an essential process in breast cancer metastasis. The aim of the present study was to determine the role of secretions of tumor-associated leukocytes (TALs) isolated from negative and positive lymph nodes (nLNs and pLNs, respectively) breast cancer patients in regulating EMT mechanism and the associated signaling pathways. We found an increased infiltration of TALs, which was associated with downregulation of E-cadherin and over-expression of vimentin in the breast carcinoma tissues of pLNs as compared to nLNs patients and normal breast tissues obtained from healthy volunteers during mammoplasty. Furthermore, TALs isolated from pLNs breast cancer patients secreted an elevated panel of cytokines by up to 2-5-fold when compared with those isolated from nLNs patients. Secretome of TALs of pLNs possessed higher TARC, IGF-1, IL-3, TNF-β, IL-5, G-CSF, IL-4, and IL-1α with more than a fivefold compared to those of nLNs. Using the human breast cancer cell lines MCF-7 and MDA-MB-231, we found that cytokines secreted by TALs isolated from nLNs and pLNs breast cancer patients promoted EMT via upregulation of TGF-β and vimentin and downregulation of E-cadherin at messenger RNA (mRNA) levels in both cell lines and at protein level in MCF-7. While TGF-β is over-expressed by MDA-MB-231 seeded in media conditioned by secretome of TALs isolated from nLNs and pLNs breast cancer patients. The downstream TGF-β signaling transcription factors, Snail, Slug, and Twist, known to be associated with EMT mechanism were over-expressed by MCF-7 and MDA-MB-231 seeded in media conditioned by secretome of TALs isolated from nLNs and pLNs breast cancer patients. Acquisition of EMT in MCF-7 cells is mechanistically attributed to the activation of EGFR and NF-κB/p65 signaling which are significantly highly expressed by MCF-7 cells seeded in media conditioned by secretome of TALs isolated from pLNs compared to nLNs patients. Overall, this study provides implications of secretome of TALs and activated EGFR and NF-κB/p65 in EMT process that may be considered a therapeutic strategy to inhibit lymph node metastasis in breast cancer patients.

show abstract

Section: Discussionsupporting

confidence: 91%

Secretome of tumor-associated leukocytes augment epithelial-mesenchymal transition in positive lymph node breast cancer patients via activation of EGFR/Tyr845 and NF-κB/p65 signaling pathway

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The induction of EMT in cultured cancer cells has been achieved using a variety of methods, including ectopic expression of transcription factors1354, growth factors35, and enzymes55, incubation with growth factors56, cytokines57, enzymes58 and androgen deprivation16. Indeed, to date, the vast majority of EMT studies in cancer have examined artificially-induced EMT-derived cells.…”

Section: Discussionmentioning

confidence: 99%

A novel spontaneous model of epithelial-mesenchymal transition (EMT) using a primary prostate cancer derived cell line demonstrating distinct stem-like characteristics

Harner-Foreman

Vadakekolathu

Laversin

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Cells acquire the invasive and migratory properties necessary for the invasion-metastasis cascade and the establishment of aggressive, metastatic disease by reactivating a latent embryonic programme: epithelial-to-mesenchymal transition (EMT). Herein, we report the development of a new, spontaneous model of EMT which involves four phenotypically distinct clones derived from a primary tumour-derived human prostate cancer cell line (OPCT-1), and its use to explore relationships between EMT and the generation of cancer stem cells (CSCs) in prostate cancer. Expression of epithelial (E-cadherin) and mesenchymal markers (vimentin, fibronectin) revealed that two of the four clones were incapable of spontaneously activating EMT, whereas the others contained large populations of EMT-derived, vimentin-positive cells having spindle-like morphology. One of the two EMT-positive clones exhibited aggressive and stem cell-like characteristics, whereas the other was non-aggressive and showed no stem cell phenotype. One of the two EMT-negative clones exhibited aggressive stem cell-like properties, whereas the other was the least aggressive of all clones. These findings demonstrate the existence of distinct, aggressive CSC-like populations in prostate cancer, but, importantly, that not all cells having a potential for EMT exhibit stem cell-like properties. This unique model can be used to further interrogate the biology of EMT in prostate cancer.

show abstract

“…The processes by which cells switch between epithelial and mesenchymal phenotypes are widely known as the epithelial-to-mesenchymal transition (EMT) and its counterpart, the mesenchymal-to-epithelial transition [139]. It is well established that inflammation promotes EMT [139,140]. Elevated levels of IL-6 in the serum have been associated with EMT and invasion along with increased size of tumours, metastasis and decreased survival of colorectal cancer patients [60].…”

Section: Invasion Metastasis and Angiogenesismentioning

confidence: 99%

Role of interleukin-6 in cancer progression and therapeutic resistance

et al. 2016

View full text Add to dashboard Cite

In the last several decades, the number of people dying from cancer-related deaths has not reduced significantly despite phenomenal advances in the technologies related to diagnosis and therapeutic modalities. The principal cause behind limitations in the curability of this disease is the reducing sensitivity of the cancer cells towards conventional anticancer therapeutic modalities, particularly in advance stages of the disease. Amongst several reasons, certain secretory factors released by the tumour cells into the microenvironment have been found to confer resistance towards chemo- and radiotherapy, besides promoting growth. Interleukin-6 (IL-6), one of the major cytokines in the tumour microenvironment, is an important factor which is found at high concentrations and known to be deregulated in cancer. Its overexpression has been reported in almost all types of tumours. The strong association between inflammation and cancer is reflected by the high IL-6 levels in the tumour microenvironment, where it promotes tumorigenesis by regulating all hallmarks of cancer and multiple signalling pathways, including apoptosis, survival, proliferation, angiogenesis, invasiveness and metastasis, and, most importantly, the metabolism. Moreover, IL-6 protects the cancer cells from therapy-induced DNA damage, oxidative stress and apoptosis by facilitating the repair and induction of countersignalling (antioxidant and anti-apoptotic/pro-survival) pathways. Therefore, blocking IL-6 or inhibiting its associated signalling independently or in combination with conventional anticancer therapies could be a potential therapeutic strategy for the treatment of cancers with IL-6-dominated signalling.

show abstract

Epithelial-to-mesenchymal transition (EMT) induced by inflammatory priming elicits mesenchymal stromal cell-like immune-modulatory properties in cancer cells

Cited by 145 publications

References 31 publications

Secretome of tumor-associated leukocytes augment epithelial-mesenchymal transition in positive lymph node breast cancer patients via activation of EGFR/Tyr845 and NF-κB/p65 signaling pathway

Secretome of tumor-associated leukocytes augment epithelial-mesenchymal transition in positive lymph node breast cancer patients via activation of EGFR/Tyr845 and NF-κB/p65 signaling pathway

A novel spontaneous model of epithelial-mesenchymal transition (EMT) using a primary prostate cancer derived cell line demonstrating distinct stem-like characteristics

Role of interleukin-6 in cancer progression and therapeutic resistance

Contact Info

Product

Resources

About