title: Galectin-3 Binding Protein Secreted by Breast Cancer Cells Inhibits Monocyte-Derived Fibrocyte Differentiation.
abstract: To metastasize, tumor cells often need to migrate through a layer of collagen-containing scar tissue which encapsulates the tumor. A key component of scar tissue and fibrosing diseases is the monocyte-derived fibrocyte, a collagen-secreting profibrotic cell. To test the hypothesis that invasive tumor cells may block the formation of the fibrous sheath, we determined whether tumor cells secrete factors that inhibit monocyte-derived fibrocyte differentiation. We found that the human metastatic breast cancer cell line MDA-MB-231 secretes activity that inhibits human monocyte-derived fibrocyte differentiation, whereas less aggressive breast cancer cell lines secrete less of this activity. Purification indicated that Galectin-3 binding protein (LGALS3BP) is the active factor. Recombinant LGALS3BP inhibits monocyte-derived fibrocyte differentiation, and immunodepletion of LGALS3BP from MDA-MB 231 conditioned media removes the monocyte-derived fibrocyte differentiation-inhibiting activity. LGALS3BP inhibits the differentiation of monocyte-derived fibrocytes from wild-type mouse spleen cells, but not from SIGN-R1(-/-) mouse spleen cells, suggesting that CD209/SIGN-R1 is required for the LGALS3BP effect. Galectin-3 and galectin-1, binding partners of LGALS3BP, potentiate monocyte-derived fibrocyte differentiation. In breast cancer biopsies, increased levels of tumor cell-associated LGALS3BP were observed in regions of the tumor that were invading the surrounding stroma. These findings suggest LGALS3BP and galectin-3 as new targets to treat metastatic cancer and fibrosing diseases.
authors.affiliation: Department of Biology, Texas A&M University, College Station, TX 77843; and.
authors.forename: Michael J V
authors.initials: MJ
authors.lastname: White
authors.affiliation: Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030.
authors.forename: David
authors.initials: D
authors.lastname: Roife
authors.affiliation: Department of Biology, Texas A&M University, College Station, TX 77843; and rgomer@tamu.edu.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Gomer
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D005260:Female; D037483:Galectin 1 / Q000378:metabolism; D037502:Galectin 3 / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; D016326:Extracellular Matrix Proteins
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D037483:Galectin 1; D037502:Galectin 3; D006023:Glycoproteins; D037181:Lectins, C-Type; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C081856:LGALS3BP protein, human; D016326:Extracellular Matrix Proteins