Collagen XV Inhibits Epithelial to Mesenchymal Transition in Pancreatic Adenocarcinoma Cells

Clementz, Anthony G.; Mutolo, Michael J.; Leir, Shih Hsing; Morris, Kirsten; Kucybala, Karolina; Harris, Henry; Harris, Ann

doi:10.1371/journal.pone.0072250

Cited by 44 publications

(50 citation statements)

References 41 publications

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“…DDRs can bind native fibrillar collagens I and III with similar affinities [2,3] but differ in their binding to non-fibrillar collagens. For instance, DDR1 can bind the collagens type IV, VIII and XV, whereas DDR2 has an increased affinity to collagen II and X [2,3,[7][8][9][10] . DDRs binding sites have been mapped and are located in the globular discoidin domain [6] .…”

Section: Introductionmentioning

confidence: 99%

The Role of Discoidin Domain Receptor 1 in Inflammation, Fibrosis and Renal Disease

Dorison

Dussaule²,

Chatziantoniou³

2017

Nephron

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Discoidin domain receptors (DDRs) are a family of 2 non-integrin collagen receptors, DDR1 and DDR2, which display a tyrosine kinase activity. They are mainly expressed during embryonic development and their role during adulthood is very limited. DDR1 has been widely studied in several types of cancers, in atherosclerosis and fibrosis, but also in chronic kidney disease (CKD). This review focuses on the role of DDR1 in chronic nephropathies and on the effect of its deletion in the pathological processes involved in renal disease progression. DDR1 was shown to be de novo expressed in several models of experimental CKD. Its genetic or pharmaco-genetic inhibition led to the preservation of renal structure and function, and to decreased inflammatory influx and fibrosis. Furthermore, delayed pharmaco-genetic inhibition of DDR1 led to significant protection in models of renal disease. These results demonstrate the involvement of DDR1 in inflammatory and fibrotic processes occurring during CKD and the beneficial effect of its inhibition. Thus, DDR1 could be an interesting therapeutic target to treat renal pathologies.

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Section: Introductionmentioning

confidence: 99%

The Role of Discoidin Domain Receptor 1 in Inflammation, Fibrosis and Renal Disease

Dorison

Dussaule²,

Chatziantoniou³

2017

Nephron

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“…However, there is currently no evidence in the field that COL15A1 itself can directly bind lipids. Second, the C-terminus of COL15A1 contains a cleavage product called restin 106 . To our knowledge the role of restin in atherosclerosis has not been previously investigated and studies are conflicting over whether this molecule is involved in angiogenesis 107,113,115,116,147 .…”

Section: Discussionmentioning

confidence: 99%

“…Certain types of integrins and discoiden domain receptors have also been shown to contribute to atherosclerotic lesion development and can act in a cell-specific manner 13,[82][83][84] . 105,106 . Structurally, the COL15A1 protein contains three distinct domains: an N-terminal non-collagenous domain, a collagenous domain, and a C-terminal non-collagenous domain 106 .…”

Section: Collagen Mediated Signalingmentioning

confidence: 99%

“…105,106 . Structurally, the COL15A1 protein contains three distinct domains: an N-terminal non-collagenous domain, a collagenous domain, and a C-terminal non-collagenous domain 106 . While the first 25 amino acids of COL15A1 is hypothesized to be a separate signaling domain, it remains to be proven whether there is a definitive function for this region 107 .…”

Section: Collagen Mediated Signalingmentioning

confidence: 99%

“…Restin is between 19-22 kilodaltons in size with a high 61% protein sequence homology to endostatin, a C-terminal cleavage product of non-fibrillar COL18A1 106,113 .…”

Section: Collagen Mediated Signalingmentioning

confidence: 99%

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"Smooth muscle cell-specific deletion of Col15a1 unexpectedly leads to impaired development of advanced atherosclerotic lesions"

Durgin

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Atherosclerotic plaque rupture or erosion with subsequent embolic events is a major cause of sudden death from myocardial infarction or stroke [1][2][3][4][5][6] . Plaque stability is classically characterized by a fibrous cap rich in ACTA2 + presumed smooth muscle cells (SMC) and collagen with a paucity of CD68 + presumed macrophages [7][8][9][10] . The dogma in the field is that SMC produce collagens that in turn provide tensile strength and stability to atherosclerotic plaques. This has largely been supported by evidence that SMC can produce collagens in vitro [11][12][13] . However, there is no direct evidence in vivo that SMC produce collagens as: 1) collagens are secreted molecules making it challenging to identify their cell source in vivo; and 2) recent lineage tracing studies by our lab [14][15][16] and others [17][18][19][20] have shown that marker genes used to identify cell type within lesions are nonspecific. For example, SMC marker genes (e.g. ACTA2) can be expressed by myeloid-derived cells and endothelial cells and SMC can express marker genes of macrophages (e.g. CD68 and LGALS3) [14][15][16][17][18][19][20] . Therefore major unanswered questions remained in the field as to whether SMC are the primary source of collagens in vivo and if SMC produced collagens in turn impact plaque development.We are interested in type XV collagen alpha 1 (COL15A1) as we identified Combined, these results provide the first direct evidence that a SMC-derived collagen, COL15A1, is critical in lesion development. IV DedicationI dedicate this to my grandfather, Arthur Labuz. You were the heart of my family and a testament to hard work, perseverance, and inner strength. I hope I have inherited an ounce of these qualities from you and have made you proud.V Acknowledgements

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Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer‐Like Phenotype

et al. 2021

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Age is a major risk factor for cancer. While the importance of age related genetic alterations in cells on cancer progression is well documented, the effect of aging extracellular matrix (ECM) has been overlooked. This study shows that the aging breast ECM alone is sufficient to drive normal human mammary epithelial cells (KTB21) to a more invasive and cancer-like phenotype, while promoting motility and invasiveness in MDA-MB-231 cells. Decellularized breast matrix from aged mice leads to loss of E-cadherin membrane localization in KTB21 cells, increased cell motility and invasion, and increased production of inflammatory cytokines and cancer-related proteins. The aged matrix upregulates cancer-related genes in KTB21 cells and enriches a cell subpopulation highly expressing epithelial-mesenchymal transition-related genes. Lysyl oxidase knockdown reverts the aged matrix-induced changes to the young levels; it relocalizes E-cadherin to cell membrane, and reduces cell motility, invasion, and cytokine production. These results show for the first time that the aging ECM harbors key biochemical, physical, and mechanical cues contributing to invasive and cancer-like behavior in healthy and cancer mammary cells. Differential response of cells to young and aged ECMs can lead to identification of new targets for cancer treatment and prevention.

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Collagen XV Inhibits Epithelial to Mesenchymal Transition in Pancreatic Adenocarcinoma Cells

Cited by 44 publications

References 41 publications

The Role of Discoidin Domain Receptor 1 in Inflammation, Fibrosis and Renal Disease

The Role of Discoidin Domain Receptor 1 in Inflammation, Fibrosis and Renal Disease

"Smooth muscle cell-specific deletion of Col15a1 unexpectedly leads to impaired development of advanced atherosclerotic lesions"

Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer‐Like Phenotype

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