| Full text | |
| Author(s): |
Noriega-Guerra, Heydi
[1]
;
Cruz, Mario C.
[2]
;
Ribeiro, Priscilla R. L.
[1]
;
Strnadel, Jan
[3, 4]
;
Wan, Huawei
[3]
;
Klemke, Richard L.
[3]
;
Jaeger, Ruy G.
[1]
;
Freitas, Vanessa M.
[1]
Total Authors: 8
|
| Affiliation: | [1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Biol Celular & Desenvolvimento, Av Prof Lineu Prestes 1524, Predio 1, Sala 428, BR-05508000 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Inst Ciencias Biomed, Ctr Facilidades Pesquisa CEFAP, Av Prof Lineu Prestes 1524, Predio 4, BR-05508000 Sao Paulo, SP - Brazil
[3] Univ Calif San Diego, Dept Pathol, 9500 Gilman Dr, MC0612, San Diego, CA 92093 - USA
[4] Comenius Univ, Jessenius Fac Med Martin, Biomed Ctr Martin JFM CU, Dept Mol Med, Mala Hora 4 C, Martin 03601 - Slovakia
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | Experimental Cell Research; v. 363, n. 2, p. 271-282, FEB 15 2018. |
| Web of Science Citations: | 2 |
| Abstract | |
Extracellular matrix (ECM) serves as a reservoir for biologically active factors, such as growth factors and proteases that influence the tumor cell behavior. ADAMTS-1 (a disintegrin and metalloprotease with thrombospondin motifs) is a secreted protease that has the ability to modify the ECM during physiological and pathological processes. Here, we analyzed the role played by ADAMTS-1 regulating HGF and TGF-beta 1 activities in the high-grade fibrosarcoma cell line (HT1080). We generated HT1080 and HEK293T cells overexpressing ADAMTS-1. HT1080 cells overexpressing ADAMTS-1 (HT1080-MPA) exhibited a significant decrease in cell proliferation and migration velocity, both in presence of HGF. We obtained similar results with wADAMTS-1-enriched conditioned medium from other cell type. However, ADAMTS-1 overexpression failed to affect TGF-beta 1 activity associated with HT1080 cell proliferation and migration velocity. Immunoblotting showed that ADAMTS-1 overexpression disturbs c-Met activation upon HGF stimulation. Downstream ERK1/2 and FAK signaling pathways are also influenced by this protease. Additionally, ADAMTS-1 decreased the size of the fibrosarcospheres, both under normal conditions and in the presence of HGF. Likewise, in presence of HGF, ADAMTS-1 overexpression in HT1080 disrupted microtumors formation in vivo. These microtumors, including individual cells, presented characteristics of non-invasive lesions (rounded morphology). Our results suggest that ADAMTS-1 is involved in regulating HGF-related functions on fibrosarcoma cells. This protease may then represent an endogenous mechanism in controlling the bioavailability of different growth factors that have a direct influence on tumor cell behavior. (AU) | |
| FAPESP's process: | 10/07699-1 - Protease ADAMTS1 influencing breast cancer behavior and microenvironment |
| Grantee: | Vanessa Morais Freitas |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 15/02498-1 - Biological significance of stress on the modulation of the tumor-stemness phenotype |
| Grantee: | Vanessa Morais Freitas |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 12/24108-2 - Role of ADAMTS-1 in local and systemic invasion of fibrosarcoma cells |
| Grantee: | Heydi Noriega Guerra |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |