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Interleukin 8 in Human Hepatocellular Carcinoma Correlates With Cancer Cell Invasion of Vessels But Not With Tumor Angiogenesis

Course of Advanced Therapeutics, Field of Oncology, Department of Surgical Oncology and Digestive Surgery, Kagoshima University Graduate School of Medicine and Dental Sciences, 8-35-1 Sakuragaoka Kagoshima, 890-8520, Japan

Correspondence: Address correspondence and reprint requests to: Fumitake Kubo, MD; E-mail: f-kubo{at}m3.kufm.kagoshima-u.ac.jp.

Background: Angiogenic factor seems necessary for the development of hepatocellular carcinoma (HCC), which is a hypervascular malignancy. This study examined the expression of interleukin (IL)-8, a potent angiogenic factor, in HCC samples.

Methods: We measured IL–8 expression by using reverse transcriptase-polymerase chain reaction in clinical HCC tissues from 45 patients who underwent surgical resection. We then assessed correlations between IL–8 expression and microvessel growth or clinicopathologic factors. We also elucidated the in vitro effect of IL–8 on HepG2 development by using fluorometric assays of proliferation, chemotaxis, and invasion.

Results: The expression of IL–8 did not significantly correlate with the microvessel count in HCC tissues, but the incidence of microscopic vessel invasion was significantly higher in IL–8–positive than in IL–8–negative tissues. Thus, more IL–8 was expressed in HCCs at pathologic stage III/IV than in those at stage I/II. Assays in vitro showed that IL–8 stimulates HepG2 chemotactic and invasive activities rather than cell proliferation.

Conclusions: The expression of IL–8 in human HCC has more relevance to metastatic potential, such as vessel invasion, than to angiogenesis or cell proliferation.

Key Words: Interleukin 8 • Hepatocellular carcinoma • Tumor progression • Angiogenesis • Chemotaxis • Vessel invasion

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