Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1α in ameloblastoma

Fuchigami, Takao; Kibe, Toshiro; Koyama, Hirofumi; Kishida, Shosei; Iijima, Mikio; Nishizawa, Yoshiaki; Hara, Hiroshi; Fujii, Tomomi; Ueda, Masahiro; Nakamura, Norifumi; Kiyono, Tohru; Kishida, Michiko

doi:10.1016/j.bbrc.2014.07.137

Cited by 21 publications

(40 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Upon damage, the epithelium secretes inflammatory cytokines such as EGF, IL-1β and IL-1α. IL-1α has been shown to induce IL-6 and CXCL8 in fibroblasts 28. Importantly, IL-6 and CXCL8 secretion from primary MRC-5 human lung fibroblasts are increased upon coculturing these cells with human bronchial epithelial cells.…”

Section: Discussionmentioning

confidence: 98%

A pro-inflammatory role for the Frizzled-8 receptor in chronic bronchitis

Spanjer¹,

Menzen

Dijkstra

et al. 2016

Thorax

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 98%

A pro-inflammatory role for the Frizzled-8 receptor in chronic bronchitis

Spanjer¹,

Menzen

Dijkstra

et al. 2016

Thorax

View full text Add to dashboard Cite

show abstract

“…Most recently, a study reported that IL‐6 secreted by AM‐derived fibroblasts cultured in vitro may play a role in the reciprocal cell‐to‐cell interaction between AM tumor cells and stromal fibroblasts ; however, there remains a lack of direct evidence whether and how this cytokine contributes to the pathogenesis of AM. In this study, we have provided first line of evidence, both in vitro and in vivo, that: (a) AM‐MSCs produced an abundant amount of IL‐6; (b) AM‐EpiCs, in response to IL‐6 stimulation or coculture with their stromal counterparts, underwent EMT characterized by altered expression of E‐cadherin, vimentin, SLUG, and TWIST, and showed increased expression of several stem cell‐related functional genes.…”

Section: Discussionmentioning

confidence: 99%

“…Interleukin (IL)‐6, one of the key cytokines produced by stromal cells within the tumor microenvironment (TME), exerts versatile effects on tumor growth via multiple mechanisms, including facilitating the EMT process, CSC‐like cell formation, and angiogenesis . A recent study has shown that reciprocal cell–cell interaction between AM tumor cells and stromal fibroblasts via IL‐1α‐stimulated secretion of IL‐6 and IL‐8 may have contributed to the TME to support the progression of AM ; however, the underlying cellular and molecular mechanisms remain largely unknown. Furthermore, the histologic features of AM comprise of proliferating odontogenic epithelium among a fibrous stroma, raising the potential biological effect of stroma on tumor behaviors.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stromal Cell-Derived Interleukin-6 Promotes Epithelial–Mesenchymal Transition and Acquisition of Epithelial Stem-Like Cell Properties in Ameloblastoma Epithelial Cells

et al. 2017

View full text Add to dashboard Cite

Epithelial-mesenchymal transition (EMT), a biological process associated with cancer stem-like or cancer-initiating cell formation, contributes to the invasiveness, metastasis, drug resistance, and recurrence of the malignant tumors; it remains to be determined whether similar processes contribute to the pathogenesis and progression of ameloblastoma (AM), a benign but locally invasive odontogenic neoplasm. Here, we demonstrated that EMT- and stem cell-related genes were expressed in the epithelial islands of the most common histologic variant subtype, the follicular AM. Our results revealed elevated interleukin (IL)-6 signals that were differentially expressed in the stromal compartment of the follicular AM. To explore the stromal effect on tumor pathogenesis, we isolated and characterized both mesenchymal stromal cells (AM-MSCs) and epithelial cells (AM-EpiCs) from follicular AM and demonstrated that, in in vitro culture, AM-MSCs secreted a significantly higher level of IL-6 as compared to the counterpart AM-EpiCs. Furthermore, both in vitro and in vivo studies revealed that exogenous and AM-MSC-derived IL-6 induced the expression of EMT- and stem cell-related genes in AM-EpiCs, whereas such effects were significantly abrogated either by a specific inhibitor of STAT3 or ERK1/2, or by knockdown of Slug gene expression. These findings suggest that AM-MSC-derived IL-6 promotes tumor-stem like cell formation by inducing EMT process in AM-EpiCs through STAT3 and ERK1/2-mediated signaling pathways, implying a role in the etiology and progression of the benign but locally invasive neoplasm. Stem Cells 2017;35:2083-2094.

show abstract

“…We found that the expression and release of RANKL by AM-1 cells, an ameloblastoma cell line, appeared to be too low to activate osteoclasts, even in the presence of other cell types such as fibroblasts. Many reports have highlighted the importance of the tumor-stroma interaction in tumor cell invasion, and the role of osteoclastogenesis in odontogenic tumors; however, no increases in RAW264.7 differentiation or RANKL expression in AM-1 were observed in cocultures with AM-1 or KD cells, respectively (26)(27)(28)(29)(30). In fact, Kumamoto and Ooya (31) reported little expression of RANKL in either plexiform or follicular ameloblastoma specimens.…”

Section: Discussionmentioning

confidence: 99%

Surface vacuolar ATPase in ameloblastoma contributes to tumor invasion of the jaw bone

Yoshimoto

Morita

Matsubara

et al. 2016

International Journal of Oncology

View full text Add to dashboard Cite

Ameloblastoma is the most common benign odontogenic tumor in Japan. It is believed that it expands in the jaw bone through peritumoral activation of osteoclasts by receptor activator of nuclear factor kappa-B ligand (RANKL) released from the ameloblastoma, as in bone metastases of cancer cells. However, the clinical features of ameloblastoma, including its growth rate and patterns of invasion, are quite different from those of bone metastasis of cancer cells, suggesting that different underlying mechanisms are involved. Therefore, in the present study, we examined the possible mechanisms underlying the invasive expansion of ameloblastoma in the jaw bone. Expression levels of RANKL assessed by western blotting were markedly lower in ameloblastoma (AM-1) cells than in highly metastatic oral squamous cell carcinoma (HSC-3) cells. Experiments coculturing mouse macrophages (RAW264.7) with AM-1 demonstrated low osteoclastogenic activity, as assessed by tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cell formation, probably because of low release of RANKL, whereas cocultures of RAW264.7 with HSC-3 cells exhibited very high osteoclastogenic activity. Thus, RANKL release from AM-1 appeared to be too low to generate osteoclasts. However, AM-1 cultured directly on calcium phosphate-coated plates formed resorption pits, and this was inhibited by application of bafilomycin A1. Furthermore, vacuolar-type H+-ATPase (V-ATPase) and H+/Cl- exchange transporter 7 (CLC-7) were detected on the surface of AM-1 cells by plasma membrane biotinylation and immunofluorescence analysis. Immunohistochemical analysis of clinical samples of ameloblastoma also showed plasma membrane-localized V-ATPase and CLC-7 in the epithelium of plexiform, follicular and basal cell types. The demineralization activity of AM-1 was only 1.7% of osteoclasts demineralization activity, and the growth rate was 20% of human normal skin keratinocytes and HSC-3 cells. These results suggest that the slow expansion of several typical types of ameloblastomas in jaw bone is attributable to its slow growth and low demineralization ability.

show abstract

Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1α in ameloblastoma

Cited by 21 publications

References 35 publications

A pro-inflammatory role for the Frizzled-8 receptor in chronic bronchitis

A pro-inflammatory role for the Frizzled-8 receptor in chronic bronchitis

Mesenchymal Stromal Cell-Derived Interleukin-6 Promotes Epithelial–Mesenchymal Transition and Acquisition of Epithelial Stem-Like Cell Properties in Ameloblastoma Epithelial Cells

Surface vacuolar ATPase in ameloblastoma contributes to tumor invasion of the jaw bone

Contact Info

Product

Resources

About