title: Reciprocal interaction between carcinoma-associated fibroblasts and squamous carcinoma cells through interleukin-1α induces cancer progression.
abstract: Crosstalk between cancer cells and carcinoma-associated fibroblasts (CAFs) has earned recognition as an interaction that plays a pivotal role in carcinogenesis. Thus, we attempted to clarify whether increase in the level of CAFs promotes cancer progression by proportionally enhancing the interaction between cancer cells and CAFs. We first analyzed clinical correlation between the levels of fibroblasts and cancer progression and found that the level of CAFs made a noticeable difference on the prognosis of patients with oral squamous cell carcinoma (OSCC). In vivo animal study also demonstrated that tumor volume depended on the dose of CAFs that was co-injected with OSCC cells. The same tendency was observed in an in vitro study. We also found that interleukin-1α (IL-1α) secreted from OSCC cells had dual effects on CAFs: IL-1α not only promoted the proliferation of CAFs but also upregulated the secretion of cytokines in CAFs such as CCL7, CXCL1, and IL-8. The induction activity of cytokine secretion by IL-1α surpassed that of proliferation in OSCC cells. In summary, we unraveled an important interactive mechanism of carcinogenesis: IL-1α released from carcinoma stimulates the proliferation of CAFs and the simultaneous increase in cytokine secretion from CAFs promotes cancer progression in human OSCC. On the basis of these findings, we propose that the level of CAFs is eligible for being selected as a prognostic factor that will be useful in routine diagnosis. We also propose that blockage of reciprocal interaction between cancer cells and CAFs will provide an insight for developing novel chemotherapeutic strategy.
authors.affiliation: Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, Korea.
authors.forename: Jung Yoon
authors.initials: JY
authors.lastname: Bae
authors.affiliation: Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, Korea.
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Yang
authors.affiliation: Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, Korea.
authors.forename: Xianglan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, Korea.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Park
authors.affiliation: Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, Korea.
authors.forename: Doo Young
authors.initials: DY
authors.lastname: Lee
authors.affiliation: Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, Korea.
authors.forename: Chung Min
authors.initials: CM
authors.lastname: Che
authors.affiliation: Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D053208:Kaplan-Meier Estimate; D008297:Male; D008807:Mice, Inbred BALB C; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009130:Muscle, Smooth / Q000737:chemistry; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000199:Actins; D016207:Cytokines; D053582:Interleukin-1alpha
keywords: cancer progression; carcinoma-associated fibroblasts; interleukin-1 alpha; oral squamous cell carcinoma; reciprocal interaction