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

Abstract

BackgroundGalectin-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.MethodsIn 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.ResultsIn 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.ConclusionsTaken 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2679-1) contains supplementary material, which is available to authorized users.

Pediatric Ependymoma: A Proteomics Perspective

“…In our study, galectins 1, 3, 8, 9 and 9b were found to be present in our analyzed series of patients. Due to their unique structure, galectins can oligomerize forming lattices upon binding to multivalent oligossacharides and influence several pathological events, such as tumorigenesis, invasion and metastasis (24) Peroxiredoxins I-VI have recently been shown to have a role in the tumorigenesis of astrocytic brain tumors (25,26). The presence of all perixoredoxin molecules, except for peroxideroxin-3, was noted in our studied ependymoma samples, in contrast to Haapasalo et al who reported absence of perixiredoxin 4 (26).…”

Elevated soluble Galectin-3 as a marker of chemotherapy efficacy in Breast cancer patients; a prospective study

“…Few comparative studies have been found that distinguish between stromal and plasma Gal-3 levels in the settings of neo-adjuvant versus adjuvant taxane treatment, especially in patients with no prior treatment history. Some studies specified parameters within which Gal-3 was examined, such as in vitro, in vivo, post-chemotherapy [8] and no chemotherapy [7,19]. Many of the studies however used more relaxed parameters for Additionally, it has been shown to bind to 11 and CD11b/ 18 integrins [9,30].…”

“…Furthermore, downregulation of intracellular Gal-3 has been associated with metastasis in breast [7,18] and gastric [19] cancers. particular study found Gal-3 in the media from cancer cells after p53 activation [20], indicating possible role in cell cycle regulation or apoptosis.…”

Galectin-3 Regulates the Expression of Tumor Glycosaminoglycans and Increases the Metastatic Potential of Breast Cancer

“…e iliac crest bone marrow samples were collected from Balb/c female Lgals3 +/+ and Lgals3 − /− previously inoculated with 4T1-scramble and 4T1-shRNA-Gal-3 cells, as described previously [23] and were fixed in 4% PFA for 24 hours. After this period, samples were decalcified in EDTA 20% during 14 days and embedded in paraffin.…”

“…Our previous studies have shown that primary breast tumors were more aggressive and had a greater potential to metastasize to the bone marrow when injected subcutaneously in Galectin-3 knockout (Lgals3 − /− ) mice [23]. ese data suggested that Gal-3 plays a central role, at least in part, in the structural organization of tissues acting as a physical barrier to control cell dissemination.…”