Human papillomavirus capsids preferentially bind and infect tumor cells. Issue 4 (27th October 2015)

• Record Type: Journal Article
• Authors: Kines, Rhonda C.; Cerio, Rebecca J.; Roberts, Jeffrey N.; Thompson, Cynthia D.; de Los Pinos, Elisabet; Lowy, Douglas R.; Schiller, John T.
• Is Part Of: International journal of cancer. Volume 138:Issue 4(2016:Feb. 15)
• Page Start: 901
• Page End: 911
• Publication Date: 2015-10-27
• Subjects: human papillomavirus -- heparan sulfate proteoglycans -- tumor tropism; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.29823
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : We previously determined that human papillomavirus (HPV) virus‐like particles (VLPs) and pseudovirions (PsV) did not, respectively, bind to or infect intact epithelium of the cervicovaginal tract. However, they strongly bound heparan sulfate proteoglycans (HSPG) on the basement membrane of disrupted epithelium and infected the keratinocytes that subsequently entered the disrupted site. We here report that HPV capsids (VLP and PsV) have the same restricted tropism for a wide variety of disrupted epithelial and mesothelial tissues, whereas intact tissues remain resistant to binding. However, the HPV capsids directly bind and infect most tumor‐derived cell lines in vitro and have analogous tumor‐specific properties in vivo, after local or intravenous injection, using orthotopic models for human ovarian and lung cancer, respectively. The pseudovirions also specifically infected implanted primary human ovarian tumors. Heparin and ι‐carrageenan blocked binding and infection of all tumor lines tested, implying that tumor cell binding is HSPG‐dependent. A survey using a panel of modified heparins indicates that N‐sulfation and, to a lesser degree, O‐6 sulfation of the surface HSPG on the tumors are important for HPV binding. Therefore, it appears that tumor cells consistently evolve HSPG modification patterns that mimic the pattern normally found on the basement membrane but not on the apical surfaces of normal epithelial or mesothelial cells. Consequently, appropriately modified HPV VLPs and/or PsV could be useful reagents to detect and potentially treat a remarkably broad spectrum of cancers. Abstract : What's new? A virus best known as a cancer villain could be made to take on the role of hero. HPV capsids – the protein coat without the viral DNA – will infect cancer cells, but steer clear of healthy tissue. By testing a panel of 60 cancer cell lines and various mouse tumor models, these authors show that the HPV particles can infect a broad range of cancer cell types by binding to the cell surface polysaccharide HSPG. This appears a promising strategy to deliver cancer treatment to a variety of tumor types.