American Association for Cancer Research
00085472can152556-sup-155599_1_supp_3685721_8gh8nk.docx (239.39 kB)

Supplementary Tables from Transcriptional Induction of Periostin by a Sulfatase 2–TGFβ1–SMAD Signaling Axis Mediates Tumor Angiogenesis in Hepatocellular Carcinoma

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journal contribution
posted on 2023-03-31, 00:13 authored by Gang Chen, Ikuo Nakamura, Renumathy Dhanasekaran, Eriko Iguchi, Ezequiel J. Tolosa, Paola A. Romecin, Renzo E. Vera, Luciana L. Almada, Alexander G. Miamen, Roongruedee Chaiteerakij, Mengtao Zhou, Michael K. Asiedu, Catherine D. Moser, Shaoshan Han, Chunling Hu, Bubu A. Banini, Abdul M. Oseini, Yichun Chen, Yong Fang, Dongye Yang, Hassan M. Shaleh, Shaoqing Wang, Dehai Wu, Tao Song, Ju-Seog Lee, Snorri S. Thorgeirsson, Eric Chevet, Vijay H. Shah, Martin E. Fernandez-Zapico, Lewis R. Roberts

Supplementary Table 1 List of antibodies, reagents and kits used in the study Supplementary Table 2 List of primers used in the study Supplementary Table 3 Comprehensive literature search of angiogenic regulators in HCC Supplementary Table 4 Correlation of 178 genes related to angiogenesis in HCC with SULF2 expression in human HCC microarray gene analysis




Mayo Clinic Cancer Center


National Natural Science Foundation of China



Existing antiangiogenic approaches to treat metastatic hepatocellular carcinoma (HCC) are weakly effectual, prompting further study of tumor angiogenesis in this disease setting. Here, we report a novel role for sulfatase 2 (SULF2) in driving HCC angiogenesis. Sulf2-deficient mice (Sulf2 KO) exhibited resistance to diethylnitrosamine-induced HCC and did not develop metastases like wild-type mice (Sulf2 WT). The smaller and less numerous tumors formed in Sulf2 KO mice exhibited a markedly lower microvascular density. In human HCC cells, SULF2 overexpression increased endothelial proliferation, adhesion, chemotaxis, and tube formation in a paracrine fashion. Mechanistic analyses identified the extracellular matrix protein periostin (POSTN), a ligand of αvβ3/5 integrins, as an effector protein in SULF2-induced angiogenesis. POSTN silencing in HCC cells attenuated SULF2-induced angiogenesis and tumor growth in vivo. The TGFβ1/SMAD pathway was identified as a critical signaling axis between SULF2 and upregulation of POSTN transcription. In clinical HCC specimens, elevated levels of SULF2 correlated with increased microvascular density, POSTN levels, and relatively poorer patient survival. Together, our findings define an important axis controlling angiogenesis in HCC and a mechanistic foundation for rational drug development. Cancer Res; 77(3); 632–45. ©2016 AACR.