TY - JOUR
T1 - Microenvironment proteinases, proteinase-activated receptor regulation, cancer and inflammation
AU - Eftekhari, Rahil
AU - De Lima, Stacy G.
AU - Liu, Yu
AU - Mihara, Koichiro
AU - Saifeddine, Mahmoud
AU - Noorbakhsh, Farshid
AU - Scarisbrick, Isobel A.
AU - Hollenberg, Morley D.
N1 - Funding Information:
The Johnson & Johnson Alberta Health Innovation Partnership (JAHIP) Prostate Cancer Research Fund/University Hospital Foundation, University of Alberta Hospital, Funder Id: Grant Number: Prostate Proteases, Protease-Activated Receptors. Canadian Institutes of Health Research, Funder Id: 10.13039/501100000024, Grant Number: 201603PJT-363434-PJT-CBBA-13135.
Funding Information:
Funding: The Johnson & Johnson Alberta Health Innovation Partnership (JAHIP) Prostate Cancer Research Fund/ University Hospital Foundation, University of Alberta Hospital, Funder Id: Grant Number: Prostate Proteases, Protease-Activated Receptors. Canadian Institutes of Health Research, Funder Id: 10.13039/501100000024, Grant Number: 201603PJT-363434-PJT-CBBA-13135.
Funding Information:
Acknowledgements: Supported by the Telus Calgary Ride for Dad-Prostate Cancer Fight Foundation, the Edmonton Janssen Research Foundation and the Canadian Institutes of Health Research (CIHR). These studies were also supported in part by the National Institute of Neurological Disorders and Stroke, Funder Id: 10.13039/100000065, Grant Number: R01NS052741 and Funder Id: 10.13039/100001770, Grant Number: RG3367 from the National Multiple Sclerosis Society to I.A.S. The expert assistance of the Snyder Institute live cell imaging facility is also gratefully acknowledged.
PY - 2018/9/25
Y1 - 2018/9/25
N2 - We propose that in the microenvironment of inflammatory tissues, including tumours, extracellular proteinases can modulate cell signalling in part by regulating proteinase-activated receptors (PARs). We have been exploring this mechanism in a variety of inflammation and tumour-related settings that include tumour-derived cultured cells from prostate and bladder cancer, as well as immune inflammatory cells that are involved in the pathology of inflammatory diseases including multiple sclerosis. Our work showed that proteinase signalling via the PARs affects prostate and bladder cancer-derived tumour cell behaviour and can regulate calcium signalling in human T-cell and macrophage-related inflammatory cells as well as in murine splenocytes. Further, we found that the tumour-derived prostate cancer cells and immune-related cells (Jurkat, THP1, mouse splenocytes) can produce PAR-regulating proteinases (including kallikreins: kallikrein-related peptidases), that can control tissue function by both a paracrine and autocrine mechanism. We suggest that this PAR-driven signalling process involving secreted microenvironment proteinases can play a key role in cancer and inflammatory diseases including multiple sclerosis.
AB - We propose that in the microenvironment of inflammatory tissues, including tumours, extracellular proteinases can modulate cell signalling in part by regulating proteinase-activated receptors (PARs). We have been exploring this mechanism in a variety of inflammation and tumour-related settings that include tumour-derived cultured cells from prostate and bladder cancer, as well as immune inflammatory cells that are involved in the pathology of inflammatory diseases including multiple sclerosis. Our work showed that proteinase signalling via the PARs affects prostate and bladder cancer-derived tumour cell behaviour and can regulate calcium signalling in human T-cell and macrophage-related inflammatory cells as well as in murine splenocytes. Further, we found that the tumour-derived prostate cancer cells and immune-related cells (Jurkat, THP1, mouse splenocytes) can produce PAR-regulating proteinases (including kallikreins: kallikrein-related peptidases), that can control tissue function by both a paracrine and autocrine mechanism. We suggest that this PAR-driven signalling process involving secreted microenvironment proteinases can play a key role in cancer and inflammatory diseases including multiple sclerosis.
KW - T-cells/macrophages/splenocytes
KW - bladder cancer
KW - microenvironment proteinases
KW - multiple sclerosis
KW - prostate cancer
KW - proteinase-activated receptors (PARs)
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U2 - 10.1515/hsz-2018-0001
DO - 10.1515/hsz-2018-0001
M3 - Article
C2 - 29924723
AN - SCOPUS:85049137145
SN - 1431-6730
VL - 399
SP - 1023
EP - 1039
JO - Biological Chemistry Hoppe-Seyler
JF - Biological Chemistry Hoppe-Seyler
IS - 9
ER -