Maciej Kaczorowski1, Przemysław Biecek2, Piotr Donizy3, Małgorzata Pieniążek4, Rafał Matkowski5,6, Agnieszka Hałoń3,6. 1. Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Wroclaw, Poland maciejdkaczorowski@gmail.com. 2. Faculty of Mathematics and Information Science, Warsaw University of Technology, Warsaw, Poland. 3. Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Wroclaw, Poland. 4. Department of Clinical Oncology, Tadeusz Koszarowski Regional Oncology Centre, Opole, Poland. 5. Division of Surgical Oncology, Department of Oncology, Wroclaw Medical University, Wroclaw, Poland. 6. Wroclaw Comprehensive Cancer Center, Wroclaw, Poland.
Abstract
BACKGROUND: RhoA and its downstream effectors Rho-associated coiled-coil kinases (ROCK) 1 and 2 are central controllers of cytoskeleton dynamics, and therefore influence cell shape, adhesion and migration. Since modulation of these processes holds promise for an effective anticancer strategy, effects of ROCK inhibition have been evaluated in a number of malignancies. MATERIALS AND METHODS: Using immunohistochemistry, ROCK1 and ROCK2 expression was semi-quantitatively assessed in 129 patient-derived primary melanomas. RESULTS: There was a striking predilection for low melanocytic expression of both kinases in thick, ulcerated and mitogenic tumors, as well as in nodular histological type. ROCK1 and -2 expression in tumor-infiltrating lymphocytes (TILs) was preferentially down-regulated in advanced and aggressive tumors. Moreover, diminished ROCK2 reactivity in melanoma cells and TILs was associated with shorter melanoma-specific and recurrence-free survival. CONCLUSION: This is the first analysis of ROCK1 and -2 protein expression in clinical melanoma samples and the results indicated the suppression of ROCK signaling in melanocytes of aggressive and late-stage tumors. Functional models that more accurately represent the clinical setting are necessary to dissect the role of ROCK1 and -2 in melanoma. Additionally, our study indicates that ROCK activity in TILs may be involved in the pathogenesis of cancer, and thus merits further investigations. Copyright
BACKGROUND:RhoA and its downstream effectors Rho-associated coiled-coil kinases (ROCK) 1 and 2 are central controllers of cytoskeleton dynamics, and therefore influence cell shape, adhesion and migration. Since modulation of these processes holds promise for an effective anticancer strategy, effects of ROCK inhibition have been evaluated in a number of malignancies. MATERIALS AND METHODS: Using immunohistochemistry, ROCK1 and ROCK2 expression was semi-quantitatively assessed in 129 patient-derived primary melanomas. RESULTS: There was a striking predilection for low melanocytic expression of both kinases in thick, ulcerated and mitogenic tumors, as well as in nodular histological type. ROCK1 and -2 expression in tumor-infiltrating lymphocytes (TILs) was preferentially down-regulated in advanced and aggressive tumors. Moreover, diminished ROCK2 reactivity in melanoma cells and TILs was associated with shorter melanoma-specific and recurrence-free survival. CONCLUSION: This is the first analysis of ROCK1 and -2 protein expression in clinical melanoma samples and the results indicated the suppression of ROCK signaling in melanocytes of aggressive and late-stage tumors. Functional models that more accurately represent the clinical setting are necessary to dissect the role of ROCK1 and -2 in melanoma. Additionally, our study indicates that ROCK activity in TILs may be involved in the pathogenesis of cancer, and thus merits further investigations. Copyright
Authors: Przemysław Podstawski; Marcin Samiec; Maria Skrzyszowska; Tomasz Szmatoła; Ewelina Semik-Gurgul; Katarzyna Ropka-Molik Journal: Int J Mol Sci Date: 2022-02-10 Impact factor: 5.923