Kim Eun Kyoung, Moon Sook, Kim Do Kyeong, Zhang Xianglan, Kim Jin
Oral Cancer Research Institute, Department of Oral Pathology, Yonsei University College of Dentistry, Seoul, Republic of Korea.
Department of Dental hygiene, College of nursing Healthcare, Sorabol college, Gyeongju, Republic of Korea.
PLoS One. 2018 Jan 23;13(1):e0188847. doi: 10.1371/journal.pone.0188847. eCollection 2018.
Cancer-associated fibroblasts (CAFs) have emerged as one of the main factors related to cancer progression, however, the conversion mechanism of normal fibroblasts (NOFs) to CAFs has not been well elucidated. The aim of this study was to investigate the underlying mechanism of CAF transformation from NOFs in oral squamous cell carcinoma (OSCC). This study found that NOFs exposed to OSCC cells transformed to senescent cells. The cytokine antibody array showed the highest secretion levels of IL-6 and CXCL1 in NOFs co-cultured with OSCC cells. Despite that both IL-6 and CXCL1 induced the senescent phenotype of CAFs, CXCL1 secretion showed a cancer-specific response to transform NOFs into CAFs in OSCC, whereas IL-6 secretion was eventuated by common co-culture condition. Further, CXCL1 was released from NOFs co-cultured with OSCC cells, however, CXCL1 was undetectable in mono-cultured NOFs or co-cultured OSCC cells with NOFs. Taken together, this study demonstrates that CXCL1 can transform NOFs into senescent CAFs via an autocrine mechanism. These data might contribute to further understanding of CAFs and to development of a potential therapeutic approach targeting cancer cells-CAFs interactions.
癌症相关成纤维细胞（CAFs）已成为与癌症进展相关的主要因素之一，然而，正常成纤维细胞（NOFs）向CAFs的转化机制尚未得到充分阐明。本研究的目的是探讨口腔鳞状细胞癌（OSCC）中NOFs向CAFs转化的潜在机制。本研究发现，暴露于OSCC细胞的NOFs会转化为衰老细胞。细胞因子抗体阵列显示，与OSCC细胞共培养的NOFs中IL-6和CXCL1的分泌水平最高。尽管IL-6和CXCL1都诱导了CAFs的衰老表型，但CXCL1的分泌显示出在OSCC中将NOFs转化为CAFs的癌症特异性反应，而IL-6的分泌是由普通共培养条件导致的。此外，CXCL1是从与OSCC细胞共培养的NOFs中释放出来的，然而，在单培养的NOFs或与NOFs共培养的OSCC细胞中未检测到CXCL1。综上所述，本研究表明CXCL1可以通过自分泌机制将NOFs转化为衰老的CAFs。这些数据可能有助于进一步了解CAFs，并有助于开发针对癌细胞与CAFs相互作用的潜在治疗方法。
