Shirakawa Kenji, Nakazato Ryota, Hara Tetsuhiro, Uemura Kenichiro, Ijaz Faryal, Takahashi Shinya, Ikegami Koji
Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Department of Anatomy and Developmental Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Med Mol Morphol. 2025 Mar 12. doi: 10.1007/s00795-025-00428-0.
Primary cilia are hair-like projections that protrude on most of mammalian cells and mediate reception of extracellular signals. Numerous studies have demonstrated that a variety of cancer cells including pancreatic ductal adenocarcinoma (PDAC) fail to form primary cilia. The loss of primary cilia is thought to cause carcinogenesis and progressive cell proliferation. However, the relationship of the primary cilia loss with carcinogenesis and/or cancer malignancy remains arguable. We herein examined whether ciliogenesis was increased in a model of more progressive PDAC and investigated effects of ciliogenesis on growth of PDAC using a pancreatic cancer cell line, PANC-1. The majority of PANC-1 cells in a cell cluster grown from a solitary cell possessed primary cilia. The rate of ciliogenesis was higher in cells grown from low density than in cells grown from high density. Almost all clones passing limiting dilution culture had abilities to grow primary cilia. Compared to the parental PANC-1 cells, clones that proliferated from a solitary cell showed increase in the ciliogenesis rate. Blocking ciliogenesis suppressed cell cluster formation. Our results suggest that pancreatic cancer cells that are more resistant to a solitary condition have abilities of ciliogenesis and form tumor-like cell clusters in a primary cilia-dependent manner.
原发性纤毛是突出于大多数哺乳动物细胞表面的毛发状突起，介导细胞外信号的接收。大量研究表明，包括胰腺导管腺癌（PDAC）在内的多种癌细胞无法形成原发性纤毛。原发性纤毛的缺失被认为会导致致癌作用和细胞的进行性增殖。然而，原发性纤毛缺失与致癌作用和/或癌症恶性程度之间的关系仍存在争议。我们在此研究了在更具侵袭性的PDAC模型中纤毛发生是否增加，并使用胰腺癌细胞系PANC-1研究了纤毛发生对PDAC生长的影响。从单个细胞生长而来的细胞簇中的大多数PANC-1细胞都具有原发性纤毛。低密度培养的细胞中纤毛发生的速率高于高密度培养的细胞。几乎所有经过有限稀释培养的克隆都有能力长出原发性纤毛。与亲代PANC-1细胞相比，从单个细胞增殖而来的克隆显示纤毛发生率增加。抑制纤毛发生会抑制细胞簇的形成。我们的结果表明，对单个细胞状态更具抗性的胰腺癌细胞具有纤毛发生能力，并以原发性纤毛依赖的方式形成肿瘤样细胞簇。
