title: CRABP1 provides high malignancy of transformed mesenchymal cells and contributes to the pathogenesis of mesenchymal and neuroendocrine tumors.
abstract: CRABP1 (cellular retinoic acid binding protein 1) belongs to the family of fatty acid binding proteins. Retinoic acid binding is the only known functional activity of this protein. The role of CRABP1 in human carcinogenesis remains poorly understood. Here, for the first time we demonstrated pro-metastatic and pro-tumorigenic activity of CRABP1 in mesenchymal tumors. Further functional analysis revealed that the pro-tumorigenic effect of CRABP1 does not depend on retinoic acid binding activity. These results suggest that CRABP1 could have an alternative intracellular functional activity that contributes to the high malignancy of transformed mesenchymal cells. Microarray analysis detected CRABP1-mediated alterations in the expression of about 100 genes, including those encoding key regulatory proteins. CRABP1 is ubiquitously expressed in monophasic synovial sarcomas, while in biphasic synovial sarcomas it is expressed uniquely by the spindle cells of the aggressive mesenchymal component. High level of CRABP1 expression is associated with lymph node metastasis and poor differentiation/high grade of pancreatic neuroendocrine tumors (pNETs). Presented data suggest CRABP1 as a promising biomarker of pNETs' clinical behavior. Our results give the first evidence of pro-tumorigenic and pro-metastatic activity of CRABP1 in mesenchymal and neuroendocrine tumors.
authors.affiliation: N.N. Blokhin Russian Cancer Research Center; Moscow, Russia.
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Kainov
authors.affiliation: N.N. Blokhin Russian Cancer Research Center; Moscow, Russia.
authors.forename: Irina
authors.initials: I
authors.lastname: Favorskaya
authors.affiliation: N.N. Blokhin Russian Cancer Research Center; Moscow, Russia.
authors.forename: Vera
authors.initials: V
authors.lastname: Delektorskaya
authors.affiliation: N.N. Blokhin Russian Cancer Research Center; Moscow, Russia.
authors.forename: Galina
authors.initials: G
authors.lastname: Chemeris
authors.affiliation: N.N. Blokhin Russian Cancer Research Center; Moscow, Russia.
authors.forename: Andrei
authors.initials: A
authors.lastname: Komelkov
authors.affiliation: N.N. Blokhin Russian Cancer Research Center; Moscow, Russia.
authors.forename: Anna
authors.initials: A
authors.lastname: Zhuravskaya
authors.affiliation: N.N. Blokhin Russian Cancer Research Center; Moscow, Russia.
authors.forename: Lyubov
authors.initials: L
authors.lastname: Trukhanova
authors.affiliation: N.N. Blokhin Russian Cancer Research Center; Moscow, Russia.
authors.forename: Elina
authors.initials: E
authors.lastname: Zueva
authors.affiliation: N.N. Blokhin Russian Cancer Research Center; Moscow, Russia.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tavitian
authors.affiliation: N.N. Blokhin Russian Cancer Research Center; Moscow, Russia.
authors.forename: Natalya
authors.initials: N
authors.lastname: Dyakova
authors.affiliation: N.N. Blokhin Russian Cancer Research Center; Moscow, Russia.
authors.forename: Irina
authors.initials: I
authors.lastname: Zborovskaya
authors.affiliation: N.N. Blokhin Russian Cancer Research Center; Moscow, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Tchevkina
mesh_terms: D000328:Adult; D000368:Aged; D002461:Cell Line, Transformed; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D013584:Sarcoma, Synovial / Q000378:metabolism / Q000473:pathology*; D014212:Tretinoin / Q000378:metabolism
chemical_list: D018168:Receptors, Retinoic Acid; C082927:retinoic acid binding protein I, cellular; D014212:Tretinoin
keywords: CRABP1; metastasis; pancreatic neuroendocrine tumors; synovial sarcomas; tumorigenicity