Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA.
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA.
Cytokine Growth Factor Rev. 2019 Aug;48:11-23. doi: 10.1016/j.cytogfr.2019.07.001. Epub 2019 Jul 17.
The stroma is a main driver of metastasis and aggressiveness in pancreatic cancer (PC), one of the deadliest malignancies worldwide. Pancreatic stellate cells (PSCs) form approximately 50% of the pancreatic tumor stroma, causing desmoplasia, extracellular matrix (ECM) deposition, epithelial-to-mesenchymal transition (EMT) and metastatic spread. Furthermore, activated PSCs can remodel the pancreatic tumor microenvironment (TME) via dynamic and complex interactions and feedback loops with PC cells, thus facilitating tumor growth through various signalling and immune pathways. Hence, increased understanding of these cellular cross-talks and how they shape the TME in PC might guide the development of novel treatment approaches against this stubborn and deadly malignancy that has so far resisted therapeutic advances. In this review, we will explore the role of the stroma and PSCs in PC development, invasion and metastasis, examine their interaction with PC cells and discuss potential treatment approaches aimed at targeting PSCs in order to reprogram the pancreatic tumor environment.
基质是胰腺癌(PC)转移和侵袭性的主要驱动因素,PC 是全球最致命的恶性肿瘤之一。胰腺星状细胞(PSC)约占胰腺肿瘤基质的 50%,导致了纤维组织增生、细胞外基质(ECM)沉积、上皮间质转化(EMT)和转移扩散。此外,激活的 PSCs 可以通过与 PC 细胞的动态和复杂相互作用及反馈环重塑胰腺肿瘤微环境(TME),从而通过各种信号和免疫途径促进肿瘤生长。因此,增加对这些细胞串扰的理解以及它们如何塑造 PC 中的 TME,可能有助于指导针对这种顽固且致命的恶性肿瘤的新治疗方法的开发,迄今为止,这种恶性肿瘤一直抵制治疗进展。在这篇综述中,我们将探讨基质和 PSCs 在 PC 发展、侵袭和转移中的作用,研究它们与 PC 细胞的相互作用,并讨论旨在靶向 PSCs 以重新编程胰腺肿瘤环境的潜在治疗方法。