The deficiency of galectin-3 in stromal cells leads to enhanced tumor growth and bone marrow metastasis

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art_PEREIRA_The_deficiency_of_galectin3_in_stromal_cells_leads_2016.PDF (1.87 MB)
Citações na Scopus
12
Tipo de produção
article
Data de publicação
2016
Editora
BIOMED CENTRAL LTD
DOI
Indexadores
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
PEREIRA, Jonathas Xavier
AZEREDO, Maria Carolina Braga
MARTINS, Felipe Sa
OLIVEIRA, Felipe Leite
SANTOS, Sofia Nascimento
BERNARDES, Emerson Soares
EL-CHEIKH, Marcia Cury
Autor de Grupo de pesquisa
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Coordenadores
Organizadores
Citação
BMC CANCER, v.16, article ID 636, 9p, 2016
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background: Galectin-3 is a multifunctional beta-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. Methods: 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. Results: 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. Conclusions: 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.
Palavras-chave
4T1 breast carcinoma, Galectin-3, Bone marrow metastasis, CXCR4/CXCL12 axis
URI
https://observatorio.fm.usp.br/handle/OPI/17044
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MDR
Artigos e Materiais de Revistas Científicas - LIM/24
Artigos e Materiais de Revistas Científicas - ODS/03