Positive feedback loop between cancer stem cells and angiogenesis in hepatocellular carcinoma.
Anti-angiogenesis-related therapies have become the standard care for patients with advanced hepatocellular carcinoma (HCC), as HCC is a highly vascularized solid tumor. Unfortunately, only modest and limited efficacies are observed. Emerging evidence have attributed to the limited efficacy to the presence of cancer stem cells (CSCs) in the tumor. CSCs predominantly drives angiogenesis via releasing proangiogenic factors and exosomes. They have the ability to resistant intratumoral hypoxia via autophagy or by directly forming the tubular structure to obtain blood. On the other hand, the vascular niche in tumor microenvironment also releases growth factors via juxtacrine and paracrine mechanisms to support the growth of CSCs and maintain its stemness features. This positive feedback loop between angiogenesis and CSCs exists in liver tumor microenvironment that is responsible for the development and poor prognosis of HCC. In this review, we summarize recent advances in our understanding of the crosstalks between angiogenesis and CSCs, and their interactions in liver tumor microenvironment and their purpose that an effective anti-angiogenic therapy should also target CSCs for HCC treatment.
Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China.
Hong
H
Yao
Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China.
Nianli
N
Liu
School of Medicine, Shenzhen University, Shenzhen, Guangdong, China.
Marie C
MC
Lin
Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China; The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, China. Electronic address: Zhengjunnian@sina.com.
Junnian
J
Zheng
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D042501:Angiogenic Proteins / Q000378:metabolism*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D025461:Feedback, Physiological; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic; D015398:Signal Transduction; D059016:Tumor Microenvironment
D020533:Angiogenesis Inhibitors; D042501:Angiogenic Proteins
Angiogenesis; Cancer stem cells; Hepatocellular carcinoma; Tumor microenvironment