Identification of beta2-microglobulin as a potential target for ovarian cancer

Abstract

Ovarian cancer is one of the most lethal gynecological cancers. Antibody-based therapy has emerged as an important therapeutic approach for an increasing number of malignancies. Here, we prepared an antibody pool against SKOV3 ovarian cancer cells, which could induce apoptosis of SKOV3 cells in a dose- and time-dependent manner. Through SEREX analysis, beta 2-microglobulin (b2M) was identified as the potential target molecules of functional antibodies. The immune IgG (i-IgG) of antibody pool had little effects on other kinds of cancer cells, maybe because of the more secretion of b2M by SKOV3. Further studies indicated that specific antibody of b2M indeed also can inhibit the growth of SKOV3. In addition, overexpression of b2M could promote the growth of SKOV3 cells in vitro, by colony formation and anchorage-independent growth assay, at least partially through the activation of PI3K/Akt pathway. Thus, b2M could be a potential therapeutic target in ovarian cancer.

Salivary transcriptomic biomarkers for detection of ovarian cancer: for serous papillary adenocarcinoma

“…In this study, 7 of 20 (P<0.02; >1.2-fold) genes were validated in an independent sample set (n=56), yielding a validation rate of 35% that is comparable to our previous studies for pancreatic cancer (24.5%) [15] and breast cancer (29.6%) [16]. All the seven validated mRNAs are downregulated as compared to the control subjects, and have been reported as cancer-related genes [23][24][25][26][27][28][29][30]. Of particular interest is that B2M [27,28], IL1B [29], and AGPAT1 [30], three molecular targets of ovarian cancer as previously demonstrated, also presented as discriminatory biomarkers in saliva.…”

“…All the seven validated mRNAs are downregulated as compared to the control subjects, and have been reported as cancer-related genes [23][24][25][26][27][28][29][30]. Of particular interest is that B2M [27,28], IL1B [29], and AGPAT1 [30], three molecular targets of ovarian cancer as previously demonstrated, also presented as discriminatory biomarkers in saliva.…”

Dickkopf-3 (DKK-3) obstructs VEGFR-2/Akt/mTOR signaling cascade by interacting of β2-microglobulin (β2M) in ovarian tumorigenesis

“…Over-expression of β2M could enhance the cell growth of SKOV-3 carcinoma cells in vitro [17]. However, the exact biological mechanism underlying the anti-apoptotic effects of β2M remains to be clearly elucidated.…”

“…In addition, β2M has multiple functions in tumor development and mediates tumorigenesis, metastasis and angiogenesis [13][14][15]. Previous studies demonstrated that β2M modulates its action in vitro via increased protein kinase A (PKA)/cyclic AMP-responsive element-binding protein (CREB) phosphorylation, VEGF expression, and cell survival, including the phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) signaling pathways in human renal carcinoma cells [16,17].…”

Translational Research and Plasma Proteomic in Cancer

“…Proteomic analysis with 2-DE can simultaneously detect changes of multiple proteins in plasma often detected differentially expressed proteins are common abundant plasma proteins and their diagnostic value may be limited. Twodimensional electrophoresis (2-DE) has been used for the discovery of circulating auto-antibodies in cancer patients and annexins I and II were reported as specific antigens in sera from patients with lung [Nolen and Lokshin, 2013]; b-2 microglobulin [Yang et al, 2009] apolipoprotein [Podzielinski et al, 2013]; gene-expression in HE4 [Ferraro et al, 2013 [Du et al, 2013]; AGR2 [Li et al, 2015c]; ubiquitin ligase [Goka and Lippman, 2015]; ferritin light chain [Jezequel et al, 2012] Gastric cancer a1-antitrypsin precursor [Hsu et al, 2007]; pepsinogen C [Terasawa et al, 2014]; Cathepsin B [Ebert et al, 2005]; galectin-1/-3 [Thijssen et al, 2015]; miR-214 [Zhang et al, 2015b]; angiopoietinlike protein 2 [Yoshinaga et al, 2015]; MOR1 [Yao et al, 2015]; circular RNA [Li et al, 2015a] Liver cancer Galectin-1/-3 [Thijssen et al, 2015]; CHI3L1/MASP2 [Ding et al, 2014]; Sall4, Glypican-3, dickkopf-1 and talin-1 [Chatterjee and Mitra, 2015] …”