Abstract 2907: Extracellular matrix remodeling triggered by lysyl oxidase inhibition promote the lung adenocarcinoma to squamous cell carcinoma transition independent ofLKB1status

AbstractLKB1 is frequently mutated in human non-small cell lung cancer (NSCLC) and Lkb1 deletion in mice triggered the lung adenocarcinoma (ADC) to squamous cell carcinoma (SCC) transdifferentiation (AST) through lysyl oxidase (LOX)-dependent extracellular matrix remodeling. Here we show that pharmacological inhibition of lysyl oxidase in KrasG12D/Trp53L/L mouse model, which is known to produce lung ADC only, triggers the ADC-to-SCC transdifferentiation independent of LKB1 status. Treatments of two different inhibitors of lysyl oxidase decrease collagen deposition and promote redox accumulation, and eventually trigger the AST. Importantly, these transited SCC show strong resistance to lysyl oxidase inhibition in stark contrast to ADC. Collectively, these findings establish a new AST mouse model independent of LKB1 inactivation status.

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MicroRNA ‐mediated extracellular matrix remodeling in squamous cell carcinoma of the oral cavity

Head & Neck ◽

10.1002/hed.26686 ◽

2021 ◽

Author(s):

Gilberto Mendes Menderico Junior ◽

Thérèse Rachell Theodoro ◽

Fatima Solange Pasini ◽

Marina Menezes Ishikawa ◽

Nayara Stephânie Sousa Santos ◽

...

Keyword(s):

Extracellular Matrix ◽

Squamous Cell Carcinoma ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling

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MicroRNA-mediated Extracellular Matrix Remodeling in Squamous Cell Carcinoma of the Oral Cavity

10.21203/rs.3.rs-97307/v1 ◽

2020 ◽

Author(s):

Gilberto Mendes Menderico ◽

Thérèse Rachell Theodoro ◽

Fatima Solange Pasini ◽

Marina de Menezes Ishikawa ◽

Nayara Stephânie Sousa Santos ◽

...

Keyword(s):

Extracellular Matrix ◽

Squamous Cell Carcinoma ◽

Tumor Microenvironment ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Biological Effects ◽

Rna Extraction ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling

Abstract Background: It has been demonstrated that for oral cavity squamous cell carcinoma (SCC) as tumor thickness increases, there are lower rates of survival. Several molecular factors have been studied to determine this invasive behavior, including microRNAs, that play a role in the tumor microenvironment. Methods: The aim of this study is evaluate the role of extracellular matrix remodeling, as well as the involvement of microRNAs, in the process of oral cavity SCC carcinogenesis. This was a retrospective study with patients operated on for SCC of the oral cavity, in addition to a group of oral mucosa samples from paired patients. RNA extraction was performed, followed by complementary DNA amplification of microRNAs related to adhesion, migration, cell proliferation, apoptosis, and constituents of the extracellular matrix. We also performed immunohistochemical reactions for markers involved in the same biological processes. Results: High expression of miR-21-5p and miR-106-5p and low expression of miR-320a and miR-222-3p were predictors of malignancies and mir21-5p, individually, showed the best differentiation between the groups (AUC = 0.972). Regarding the immunohistochemical markers, there was greater expression of p53, EGFR, metalloproteinase-2 (MMP-2), laminin beta, Ki-67 and CD34 in the tumor cells than in the healthy mucosa. Furthermore, increased expression of MMP-2, metalloproteinase-9 (MMP-9), laminin alpha and laminin beta in tumor-related fibroblasts and lower continuity of type IV collagen in the basement membrane were observed. Conclusions: These results demonstrate the biological effects of microRNAs on the carcinogenesis of SCC of the oral cavity as well as the intense modification of the tumor microenvironment.

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Moderate aerobic exercise prevents matrix degradation and death in a mouse model of aortic dissection and aneurysm

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00229.2020 ◽

2021 ◽

Vol 320 (5) ◽

pp. H1786-H1801

Author(s):

Brittany O. Aicher ◽

Jackie Zhang ◽

Selen C. Muratoglu ◽

Rebeca Galisteo ◽

Allison L. Arai ◽

...

Keyword(s):

Extracellular Matrix ◽

Mouse Model ◽

Aerobic Exercise ◽

Thoracic Aortic Aneurysm ◽

Lysyl Oxidase ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

Matrix Degradation ◽

Aortic Aneurysm And Dissection ◽

Oxidase Inhibition

Moderate aerobic exercise was shown to significantly reduce mortality, extracellular matrix degradation, and thoracic aortic aneurysm and dissection formation associated with lysyl oxidase inhibition in a mouse model. Gene expression suggested a reversal of TGF-β, inflammation, and extracellular matrix remodeling pathway dysregulation, along with augmented elastogenesis with exercise.

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