Differential immunization identifies PHB1/PHB2 as blood-borne tumor antigens

Abstract

Early diagnosis of cancer is crucial for successful treatment. Noninvasive assays for detecting tumor-derived antigens in serum and other bodily fluids have the potential to screen healthy individuals for hitherto undetected cancers. Very few such assays have been successfully developed, in part because identifying potential target antigens remains a challenge. To identify new blood-borne tumor antigens for the purpose of establishing such assays, we have developed a novel technique called differential immunization. Using this method, we have identified PHB1 and PHB2, proteins thought to function as mitochondrial chaperones and transcriptional regulators, as antigens released from colorectal tumors in vivo. Serum from colorectal patients contains significantly higher levels of these antigens compared to serum from healthy volunteers. These data demonstrate that differential immunization is an effective new method for identifying tumor-derived antigens in serum.

Rescue of paclitaxel sensitivity by repression of Prohibitin1 in drug-resistant cancer cells

“…The increased expression of cell-surface PHB1 on drug-resistant cells further suggests that cell-surface PHB1 on cells in solid tumors or particularly on circulating tumor cells could provide a marker for the detection of taxane resistance in cancer patients either before or during the course of chemotherapy. PHB1 can also circulate independently and has been shown to be increased in the serum of patients with colorectal cancer (42). The relevance of this increased level of circulating PHB1 to any form of drugresistance has not yet been investigated.…”

Prohibitin-2 Binding Modulates Insulin-like Growth Factor-binding Protein-6 (IGFBP-6)-induced Rhabdomyosarcoma Cell Migration

“…PHB1 (51,53), PHB2 (56), and PHB1⅐PHB2 complexes (14,57) associate with plasma membrane lipid rafts that are believed to modulate many intracellular signaling events. Overexpression of PHB1 in 3T3-L1 fibroblasts up-regulates basal ERK MAPK signaling, leading to adipogenesis (58).…”

Up-regulation of prohibitin 1 is involved in the proliferation and migration of liver cancer cells

“…For example, decreased expression of PHB was reported in human stomach adenocarcinoma tissue compared with the surrounding normal tissues [5]. However, a number of studies report high-level expression of PHB in other tumor tissues, such as lung cancer, prostate carcinoma [6], and rat bladder carcinomas [7]. Studies have also shown that PHB levels are higher in transformed cells and tumors than in their normal counterparts [7][8][9].…”