Integrated functions of membrane‐type 1 matrix metalloproteinase in regulating cancer malignancy: Beyond a proteinase

Sakamoto, Takeharu; Seiki, Motoharu

doi:10.1111/cas.13231

Cited by 45 publications

(51 citation statements)

References 67 publications

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“…HIF promotes the expression of many genes, including MT1-MMP and MT1-MMP expression, and HIF activation might form a positive feedback loop in both mesenchymal and cancer cells. 16 These results support our data that levels of HIF-1a and MT1-MMP mRNAs significantly decrease in Anxa1-knocked down versus control Caki-1 cells (Fig. 5).…”

Section: Discussionsupporting

confidence: 90%

“…Others have shown that MT1-MMP is a key regulator of mesenchymal cell activity. 16 The same study also showed that the cytoplasmic tail of MT1-MMP binds FIH-1 and promotes a stable FIH-1-Mint3 interaction. Mint3-bound FIH cannot hydroxylate HIFa.…”

Section: Discussionmentioning

confidence: 86%

“…a), but not MMP‐2 and MMP‐9 (Fig. ), prompting us to monitor mRNA encoding HIF‐1α, a transcription factor positively regulating MT1‐MMP expression . HIF‐1α transcript levels decreased in Anxa1 knockdown relative to control Caki‐1 cells (Fig.…”

Section: Resultsmentioning

confidence: 95%

“…The present study was approved by the ethics committees of Asama General Hospital (no. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] and Shinshu University School of Medicine (no. 3627), and was undertaken in accordance with the Declaration of Helsinki.…”

Section: Introductionmentioning

confidence: 99%

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Annexin A1 expression is correlated with malignant potential of renal cell carcinoma

Yamanoi

Fujii

et al. 2018

Int J of Urology

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Objectives To evaluate the expression of annexin A1 protein in patients with renal cell carcinoma. Methods Annexin A1 expression was examined in renal cell carcinoma specimens from 27 patients, and their disease‐free survival was analyzed using the log–rank test. Annexin A1 knockdown in the human renal cell carcinoma cell line Caki‐1 was carried out, and its proliferation, invasion, motility and adhesion were compared with those of control cells. Results In 13 out of 27 patients, annexin A1 was highly expressed in the membrane of renal cell carcinoma tumor cells, whereas in the rest of the patients, annexin A1 expression was weak or negligible in the membrane of those cells. Patients with high annexin A1 expression had significantly poorer disease‐free survival than those with weak or negligible annexin A1 expression (P = 0.031). In the renal cell carcinoma cell line, annexin A1 knockdown cells showed significantly decreased proliferation, invasion, motility and adhesion relative to control cells, and expressed lower relative levels of membrane‐type 1 matrix metalloproteinase and hypoxia‐inducible factor 1‐alpha transcripts, showing a potential pathway regulated by annexin A1. Conclusion Annexin A1 is associated with renal cell carcinoma malignant potential and could serve as a marker of poor prognosis.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Annexin A1 expression is correlated with malignant potential of renal cell carcinoma

Yamanoi

Fujii

et al. 2018

Int J of Urology

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“…Specifically, protease-induced breakdown of the ECM components is essential for tumor cells to across tissue barriers [4,5]. ADAMTS (a disintegrin-like and metalloproteinase with thrombospondin motifs) is a family of extracellular metalloproteinases which was first identified in 1997.…”

Section: Introductionmentioning

confidence: 99%

Promotion of Tumor Growth by ADAMTS4 in Colorectal Cancer: Focused on Macrophages

Chen

Luo

Zhou

et al. 2018

Cell Physiol Biochem

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Background/Aims: ADAMTSs (A disintegrin and metalloprotease domains with thrombospondins motifs) are a family of extracellular proteases that have been related to both oncogenic and tumor-suppressive functions. The aim of the present study was to investigate: 1) the mutation, copy-number alterations, and expression profile of ADAMTSs in colorectal cancer and 2) whether ADAMTSs participate in colorectal cancer (CRC) progression and invasion. Methods: The mutation, copy-number alterations, and expression profile of ADAMTSs in CRC were analyzed in the TCGA cohort using cBioportal. ADAMTS4 expression in tumor tissues and cell lines were determined by immunostaining and real-time quantitative PCR. The role of ADAMTS-4 in CRC progression and the underlying mechanisms were studied by using short hairpin RNA-mediated knockdown of ADAMTS4. The effects of ADAMTS4 in cell proliferation and invasion were determined by clone formation assay and transwell migration assay, respectively. Macrophages were depleted by liposomal clodronate in immune-competent BALB/c mice and tumor growth was analyzed. Results: ADAMTS4 was differentially expressed in CRC and predicted a poor prognosis. Elevated ADAMTS4 expression was closely associated with larger tumor size, enhanced TNM stage, and a poor clinical outcome in patients with CRC. ADAMTS4 knockdown had no inhibitory implications on cell proliferation and invasion in vitro, but significantly attenuated tumor growth in vivo. Mechanistically, we revealed that ADAMTS4 was associated macrophages infiltration and polarization in the tumor microenvironment of CRC. Macrophage depletion largely abolished the promotive effect of ADAMTS4 on tumor growth in the immune competent BALB/c mice. Conclusion: ADAMTS4 seemed to be a promising prognostic indicator in CRC. The novel link between ADAMTS4 and macrophages mirrors the potential regulatory roles of ADAMTSs in the inflammatory microenvironment of cancers.

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Isolation of Highly Migratory and Invasive Cells in Three‐Dimensional Gels

2020

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We developed a modified invasion assay in three‐dimensional (3D) gels that permits isolation of invading cells as living cells, termed an invading cell–trapping (iCT) assay. A small cell strainer consisting of nylon mesh with pores of 40‐µm square is used in this assay. A layer of gel composed of extracellular‐matrix components is formed on each side of the nylon mesh, which permits cell migration or invasion from one gel layer to the other. At the end of the assay, the two gel layers are removed from the apparatus and easily separated from each other. Invading cells from the primary gel are trapped in the secondary gel, which maintains the morphology and other properties of the invasive cells in a 3D matrix. The cells that have invaded are observed and counted with a standard light microscope without cell staining. There is no need for a specialized microscope, imaging analysis software, or advanced cell‐biological technical knowledge in this assay. This assay can also reduce measurement of nonspecific cell invasion by monitoring the upward invasion of cells. The viability of both invading and non‐invading cells trapped in the gels can be assessed by typical colorimetric assays, if desired. This assessment characterizes the total number of cells (invading and non‐invading cells) and the ratio of invading cells to total cells. By repeating the iCT assay, further enrichment of invasive and noninvasive cells can be attained. Thus, this assay improves comparative analyses between invasive and noninvasive cells. © 2020 by John Wiley & Sons, Inc. Basic Protocol 1: Measuring upward cell invasion into collagen gel Basic Protocol 2: Measuring cell invasion from Matrigel into collagen gel Basic Protocol 3: Isolation and enrichment of highly invasive cells

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Integrated functions of membrane‐type 1 matrix metalloproteinase in regulating cancer malignancy: Beyond a proteinase

Cited by 45 publications

References 67 publications

Annexin A1 expression is correlated with malignant potential of renal cell carcinoma

Annexin A1 expression is correlated with malignant potential of renal cell carcinoma

Promotion of Tumor Growth by ADAMTS4 in Colorectal Cancer: Focused on Macrophages

Isolation of Highly Migratory and Invasive Cells in Three‐Dimensional Gels

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