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Overexpression of pregnancy-associated plasma protein-A in ovarian cancer cells promotes tumor growth in vivo

, : Overexpression of pregnancy-associated plasma protein-A in ovarian cancer cells promotes tumor growth in vivo. Endocrinology 152(4): 1470-1478

Pregnancy-associated plasma protein-A (PAPP-A) is an important regulatory component of the IGF system. Through proteolysis of inhibitory IGF binding proteins (IGFBPs), PAPP-A acts as a positive modulator of local IGF signaling in a variety of biological systems. A role of IGF in the progression of several common forms of human cancer is now emerging, and therapeutic intervention of IGF receptor signaling is currently being explored. However, little is known about the activities of other components of the IGF system in relation to cancer. We hypothesized that PAPP-A acts to enhance tumor growth in vivo. To test this hypothesis, we overexpressed wild-type PAPP-A or a mutant PAPP-A with markedly reduced IGFBP protease activity in SKOV3 cells, a human ovarian carcinoma cell line with low tumorigenic potential. In vitro, SKOV3 clones with elevated PAPP-A expression (PAPP-A-1, PAPP-A-28) showed accelerated anchorage-independent growth in soft agar assays compared to clones overexpressing mutant PAPP-A (E483Q-1, E483Q-5) and vector controls. PAPP-A-28, with the highest PAPP-A expression and IGFBP proteolytic activity, also had markedly increased cell invasion through Matrigel. In vivo, we found significantly accelerated tumor growth rates of PAPP-A-overexpressing SKOV3 clones compared with mutant PAPP-A and controls. Investigation of angiogenesis indicated that overexpression of PAPP-A favored development of mature tumor vasculature and that tumor precursors of PAPP-A-28 in particular had a significantly higher degree of vascularization months before obvious tumor development. In conclusion, our data show that PAPP-A proteolytic activity enhances the tumorigenic potential of ovarian cancer cells and establish a novel tumor growth-promoting role of PAPP-A.


PMID: 21303951

DOI: 10.1210/en.2010-1095

Other references

Shaĭdullin, M.S.; Rebane, A.A., 1974: Electrotherapy of hyperesthesia of the hard dental tissues. Voenno-Meditsinskii Zhurnal: 76-78

Delecolle J C.; Rieb J P., 1990: Supplementary faunistic list of the ceratopogonidae of alsace france diptera nematocera. Bulletin de la Societe Entomologique de France 95(5-6): 183-185

Scholefield, P.; Heathwaite, L.; Hodgkinson, R.; Withers, P.; Brazier, R.; Beven, K.; Walling, D.; Haygarth, P., 2007: Spatial distribution of P mobilisation in agriculture headwater catchments. Flow weighted mean concentrations and DESPRAL index values were determined for a range of headwater catchments from different geoclimatic locale across England. These values were determined through both intensive and sparse data monitoring techniq...

Chatterjee, S.N.; Payne, J.E.; Berne, T.V., 1975: Difficulties in obtaining kidneys from potential postmortem donors. Disease outcome and kidney disposition of 86 patients referred as potential postmortem kidney donors were followed up over a one-year period to determine factors that led to "organ wastage." Six patients died before fulfilling the electo...

Hohsfield, L.A.; Ammann, C.G.; Humpel, C., 2013: Inflammatory status of transmigrating primary rat monocytes in a novel perfusion model simulating blood flow. It remains unclear whether monocyte infiltration plays a protective or detrimental role in neurodegenerative disease. The present study characterizes the inflammatory status of primary monocytes in a novel in vitro perfusion model. Monocytes under...

Garret, R.; Ames, R.P., 1974: Alexander disease. Case report with electron microscopical studies and review of the literature. Archives of Pathology 98(6): 379-385

Ramjeesingh, R.; Quan, M.Lynn.; Gardner, S.; Holloway, C.M.B., 2009: Prediction of involvement of sentinel and nonsentinel lymph nodes in a Canadian population with breast cancer. We sought to identify criteria for the intraoperative assessment of sentinel lymph node (SLN) involvement in women with early breast cancer. We also sought to determine whether the SLN nomogram developed by the Memorial Sloan-Kettering Cancer Cent...

Jia, F.; Yue, M.; Chandra, D.; Homanics, G.E.; Goldstein, P.A.; Harrison, N.L., 2007: Isoflurane is a potent modulator of extrasynaptic GABA(A) receptors in the thalamus. Volatile anesthetics are used clinically to produce analgesia, amnesia, unconsciousness, blunted autonomic responsiveness, and immobility. Previous work has shown that the volatile anesthetic isoflurane, at concentrations that produce unconsciousn...

Van-Hove, L.; Delacourt, M.; Park, B.; Sobis, H.; Vandeputte, M., 1978: Presence of common surface antigens on endodermal tumors and embryonal tissues of rats hamsters and mice. Antiserum against yolk-sac carcinoma of rat was prepared in rabbits. After appropriate absorption in vitro or in vivo this antiserum was examined on different tumors and normal tissues of rat, hamster and mouse. The methods used were indirect immu...

Schlachter, E., 1964: Circulatory Stress And Treatment In Neuroleptic Medication. Therapie der Gegenwart 103: 541-552