Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Adv Exp Med Biol. 2020;1234:57-70. doi: 10.1007/978-3-030-37184-5_5.
Pancreatic cancer is one of the most challenging adenocarcinomas due to its hostile molecular behavior and complex tumor microenvironment. It has been recently postulated that pancreatic stellate cells (PSCs), the resident lipid-storing cells of the pancreas, are important components of the tumor microenvironment as they can transdifferentiate into highly proliferative myofibroblasts in the context of tissue injury. Targeting tumor-stromal crosstalk in the tumor microenvironment has emerged as a promising therapeutic strategy against pancreatic cancer progression and metastasis. This chapter brings a broad view on the biological and pathological role of PSCs in the pancreas, activated stellate cells in the onset of tissue fibrosis, and tumor progression with particular emphasis on the bidirectional interactions between tumor cells and PSCs. Further, potential therapeutic regimens targeting activated PSCs in the pre-clinical and clinical trials are discussed.
胰腺癌是最具挑战性的腺癌之一,其原因在于其具有恶性的分子行为和复杂的肿瘤微环境。最近有人提出,胰腺星状细胞(PSCs)是胰腺的固有脂质储存细胞,是肿瘤微环境的重要组成部分,因为它们在组织损伤的情况下可以向高度增殖的肌成纤维细胞转分化。针对肿瘤微环境中的肿瘤-基质相互作用已成为一种有前途的治疗策略,可以抑制胰腺癌的进展和转移。本章广泛介绍了 PSCs 在胰腺中的生物学和病理学作用、激活的星状细胞在组织纤维化发病机制中的作用,以及肿瘤进展过程中的作用,特别强调了肿瘤细胞与 PSCs 之间的双向相互作用。此外,还讨论了针对临床前和临床试验中激活的 PSCs 的潜在治疗方案。