Novel evidence indicates the presence and replication of hepatitis B virus in breast cancer tissue

Abstract

As a member of the liver tropic virus family, hepatitis B virus (HBV) was thought to only infect and replicate within the liver. Sodium taurocholate co-transporting polypeptide (NTCP) has been identified as a functional cellular receptor and a major determinant of liver tropism and HBV entry level species specificity. In the present study, the Oncomine database was used to explore differences in NTCP expression among cancerous and normal tissues. The results revealed that NTCP was highly expressed in breast cancer (BC), which was subsequently verified in clinical samples. Furthermore, in the BC tissue of patients with chronic HBV, HBV antigens, viral DNA/RNA and specific viral particles were detected via immunohistochemistry, ELISA, western blotting, reverse transcription-quantitative PCR and electron microscopy. Different HBV biomarkers and Dane particles were detected in BC. Furthermore, high levels of HBV-specific RNAs, the characteristic signals of HBV replication, were also detected, indicating that HBV infects BC tissue by binding to NTCP and replicating within. Based on the data of the present study, BC tissue may represent a second location of HBV infection and replication in addition to the liver.

Utility of Hepatic Transporters as Multimodal Gene Reporters for Cell‐Based Medicine

“…For example, OATP1B3 expression was found in various established cancer cell lines including lungs, pancreas, stomach, and colon. [ 43 ] NTCP and OATP1B3 expression was found to be associated with different types of breast cancer, [ 43,44 ] whereas OATP1B1 expression reported to be associated with colon cancers. [ 43 ] Using an omics approach, future studies should aim to elucidate global cell signaling after ectopic OATP1B3, 1B1 and NTCP expression in MSCs and other normal established cell lines.…”

Prognostic Value of Hepatitis B Virus Infection in Very Young Patients With Curatively Resected Breast Cancer: Analyses From an Endemic Area in China

“…Given that both early breast cancer and HBV are endemic in China, it is possible that HBV infection is associated with the prognosis of early breast cancer, even though the precise mechanisms are yet to be determined. It is crucial to address this issue since HBV has been reported to be found in breast cancer tissue (24). We therefore performed this study to investigate the HBsAg prevalence in very young breast cancer and the impact of HBsAg on the survival of these patients, and to establish nomograms to better predict prognosis for very young patients with breast cancer.…”

Extrahepatic carcinogenicity of oral nucleos(t)ide analogues in chronic hepatitis B carriers: A 35,000‐Korean outcome study

“…Possible carcinogenic effects of occult HBV infection in the breast are: (1) a reduction followed by a long-term rise in free oestrogen due to prolonged virus-induced hepatic necroinflammation; (2) a breast-specific effect of hepatitis B x (HBx)-interacting protein; and (3) cyclin D1 overexpression caused by HBx. 48,49 These observations may account for the decreased rate of the female breast cancer in our antiviral set. And, in terms of prostate cancer, possible cross-talk between HBV replication and the increased androgen stimulation responsible for prostate cancer may explain the protective effect of antiviral therapy.…”

“…Recent evidence indicates that HBV is tropic for breast tissues, where it may even replicate. Possible carcinogenic effects of occult HBV infection in the breast are: (1) a reduction followed by a long‐term rise in free oestrogen due to prolonged virus‐induced hepatic necroinflammation; (2) a breast‐specific effect of hepatitis B x (HBx)‐interacting protein; and (3) cyclin D1 overexpression caused by HBx 48,49 . These observations may account for the decreased rate of the female breast cancer in our antiviral set.…”