New cancer proteins raise hope for vaccine and earlier tumor detection

New cancer proteins raise hope for vaccine and earlier tumor detection

US researchers hope that their recent identification of "PL2L" cancer proteins found in all tumor stages (from pre-malignant to advanced) of many types of cancer will provide targets for a cancer vaccine, as well as new therapies and earlier detection of cancer cells.

You can read how principal investigator Dr Jian-Xin Gao from the department of pathology and the Comprehensive Cancer Center, at Ohio State University Medical Center in Columbus, and colleagues, identified the "Piwil2-like" proteins, online in the 20 October issue of the Public Library of Science journal PLoS ONE.

In 2007, Gao and his team discovered a type of pre-cancerous cell that behaves like a stem cell in that it can potentially either remain benign or become malignant, depending on what environmental signals it receives.

They found that these precancerous stem cells stably express the Piwil2 gene, which was surprising because until then it was thought this only happened in the testis and embryonic tissue.

With this latest study they found protein molecules that appear to be incomplete versions of those coded by the Piwil2 gene in humans and mice: the PL2L proteins.

They analyzed human cancer cell lines and mouse tumors and showed that the cells produced lots of PL2L proteins but not much complete Piwil2. They wrote:

"We have identified several PL2L proteins including PL2L80, PL2L60, PL2L50 and PL2L40, using combined methods of Gene -Exon-Mapping Reverse Transcription Polymerase Chain Reaction (GEM RT-PCR), bioinformatics and a group of novel monoclonal antibodies."

They established that PL2L60 rather than other PL2L proteins or complete Piwil2 was the predominant product in various types of human and mouse tumor cells and that it promoted cancer cell survival and proliferation both in culture and in live tumors, by enhancing certain gene expressions, stimulating a key part of the cell cycle, and encouraging the nuclear expression of a growth promoting protein.

"Consistently, PL2L proteins rather than Piwil2 are predominantly expressed in the cytoplasm or cytoplasm and nucleus of euchromatin-enriched tumor cells in human primary and metastatic cancers, such as breast and cervical cancers," wrote the authors.

Using novel antibodies, Gao and colleagues also found PL2L60 in many types of human cancer cells, including those of the blood, skin, kidney, brain, liver, pancreas, ovaries, lung, cervix, and soft tissues of humans and mice.

But they found mostly whole Piwil2 present in dead and dying tumor cells, suggesting it plays an opposite role in tumor development to PL2L proteins.

"Because PL2L60 is consistently expressed in many types and all stages of cancer, we believe it might play a role in tumor initiation and progression, but might be distinct from the known oncogenes and tumor suppressor genes with regard to its tumorigenic mechanism," said Gao.

"We believe we may have identified a common tumor antigen that may play a role in tumor development generally and serve as a bridge linking cancer diagnostics and anticancer drug development," he added.

"Identification of Piwil2-Like (PL2L) Proteins that Promote Tumorigenesis."

Yin Ye, De-Tao Yin, Li Chen, Quansheng Zhou, Rulong Shen, Gang He, Qingtao Yan, Zhenyu Tong, Andrew C Issekutz, Charles L Shapiro, Sanford H Barsky, Haifan Lin, Jian-Jian Li, Jian-Xin Gao.

PLoS ONE, published 20 Oct 2010.

DOI: 10.1371/journal.pone.0013406

Source: Ohio State University Medical Center.

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Section Issues On Medicine: Disease