title: The deficiency of galectin-3 in stromal cells leads to enhanced tumor growth and bone marrow metastasis.
abstract: Galectin-3 is a multifunctional β-galactoside-binding lectin that once synthesized, is expressed in the nucleus, cytoplasm, cell surface and in the extracellular environment. Because of its unique structure, galectin-3 can oligomerize forming lattice upon binding to multivalent oligossacharides and influence several pathologic events such as tumorigenesis, invasion and metastasis.
  
  
  
  In our study, balb/c Lgals3+/+ and Lgals3-/- female mice were inoculated in the fourth mammary fat pad with 4T1 breast cancer cell line. The primary tumor, inguinal lymph nodes and iliac bone marrow were evaluated 15, 21 and 28 days post-injection. The primary tumor growth was evaluated by measuring the external diameter, internal growth by ultrasound and weight of the excised tumor. The presence of cancer cells in the draining lymph nodes and iliac crest bone marrow were performed by immunohistochemistry, PCR and clonogenic metastatic assay.
  
  
  
  In this study we demonstrated that the deletion of galectin-3 in the host affected drastically the in vivo growth rate of 4T1 tumors. The primary tumors in Lgals3-/- mice displayed a higher proliferative rate (p < 0,05), an increased necrotic area (p < 0,01) and new blood vessels with a wider lumen in comparison with tumors from Lgals3+/+ mice (P < 0,05). Moreover, we detected a higher number of 4T1-derived metastatic colonies in the lymph nodes and the bone marrow of Lgals3-/- mice (p < 0,05). Additionally, healthy Lgals3-/- control mice presented an altered spatial distribution of CXCL12 in the bone marrow, which may explain at least in part the initial colonization of this organ in Lgals3-/- injected with 4T1 cells.
  
  
  
  Taken together, our results demonstrate for the first time that the absence of galectin-3 in the host microenvironment favors the growth of the primary tumors, the metastatic spread to the inguinal lymph nodes and bone marrow colonization by metastatic 4T1 tumor cells.
authors.affiliation: Programa de Pós-Graduação em Anatomia Patológica, Hospital Clementino Fraga Filho, UFRJ, Rio de Janeiro, Brazil.
authors.forename: Jonathas Xavier
authors.initials: JX
authors.lastname: Pereira
authors.affiliation: Programa de Pós-Graduação em Ciências Morfológicas, ICB, UFRJ, Rio de Janeiro, Brazil.
authors.forename: Maria Carolina Braga
authors.initials: MC
authors.lastname: Azeredo
authors.affiliation: Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Felipe Sá
authors.initials: FS
authors.lastname: Martins
authors.affiliation: Laboratório de Oncologia Experimental e Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, São Paulo, Brazil.
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
authors.affiliation: Laboratório de Proliferação e Diferenciação Celular, ICB, UFRJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Felipe Leite
authors.initials: FL
authors.lastname: Oliveira
authors.affiliation: Centro de Radiofarmácia, Instituto de Pesquisas Energéticas e Nucleares (IPEN), São Paulo, Brazil.
authors.forename: Sofia Nascimento
authors.initials: SN
authors.lastname: Santos
authors.affiliation: Centro de Radiofarmácia, Instituto de Pesquisas Energéticas e Nucleares (IPEN), São Paulo, Brazil.
authors.forename: Emerson Soares
authors.initials: ES
authors.lastname: Bernardes
authors.affiliation: Laboratório de Proliferação e Diferenciação Celular, ICB, UFRJ, Rio de Janeiro, RJ, Brazil. marcia@histo.ufrj.br.|Cidade Universitária, Ilha do Fundão, Instituto de Ciências Biomédicas, CCS, Av. Carlos Chagas Filho, 393. Bloco F, CEP. 21941-902, Rio Janeiro, RJ, Brazil. marcia@histo.ufrj.br.
authors.forename: Márcia Cury
authors.initials: MC
authors.lastname: El-Cheikh
mesh_terms: D000818:Animals; D019046:Bone Marrow Neoplasms / Q000235:genetics / Q000473:pathology* / Q000556:secondary*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D037502:Galectin 3 / Q000172:deficiency* / Q000235:genetics; D008198:Lymph Nodes; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation
chemical_list: D037502:Galectin 3; C485095:Lgals3 protein, mouse
keywords: 4T1 breast carcinoma; Bone marrow metastasis; CXCR4/CXCL12 axis; Galectin-3