title: Differential remodeling of cadherins and intermediate cytoskeletal filaments influence microenvironment of solid and ascitic sarcoma.
abstract: Different forms of sarcoma (solid or ascitic) often pose a critical medical situation for pediatric or adolescent group of patients. To date, predisposed genetic anomalies and related changes in protein expression are thought to be responsible for sarcoma development. However, in spite of genetic abnormality, role of tumor microenvironment is also indispensable for the evolving neoplasm. In our present study, we characterized the deferentially remodeled microenvironment in solid and ascitic tumors by sequential immunohistochemistry and flowcytometric analysis of E-cdaherin, N-cadherin, vimentin, and cytokeratin along with angiogenesis and metastasis. In addition, we considered flowcytometric apoptosis and CD133 positive cancer stem cell analysis. Comparative hemogram was also considered as a part. Our investigation revealed that both types of tumor promoted neovascularization over time with sign of local inflammation. Invasion of neighboring skeletal muscle by solid sarcoma was more frequent than its ascitic counterpart. In contrary, rapid and earlier cadherin switching (E-cadherin to N-cadherin) in ascitic sarcoma made them more aggressive than that of solid sarcoma and helped to early metastasize distant tissue like liver through the hematogenous route. Differential cadherin switching and infidelity of cytokeratin expression in Vimentin positive sarcoma also influenced the behavior of ascitic CD133+ cancer initiating cell pool with respect to CD133+ cells housed in solid sarcoma. Therefore our study concludes that differential cadherin switching program and infidelity of intermediate filaments in part, sharply discriminate the severity and metastatic potentiality of either type of sarcoma accompanying with CD133+ cellular repertoire. Besides, tumor phenotype-based dichotomous cadherin switching program could be exploited as a future drug target to manage decompensated malignant ascitic and solid sarcoma.
authors.affiliation: Stem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, 108, C. R. Avenue, Kolkata, 700073, West Bengal, India.
authors.forename: Malay
authors.initials: M
authors.lastname: Chaklader
authors.forename: Ankita
authors.initials: A
authors.lastname: Pan
authors.forename: Aditya
authors.initials: A
authors.lastname: Law
authors.forename: Sukalpa
authors.initials: S
authors.lastname: Chattopadhayay
authors.forename: Ritam
authors.initials: R
authors.lastname: Chatterjee
authors.forename: Sujata
authors.initials: S
authors.lastname: Law
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D001201:Ascites / Q000378:metabolism* / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism*; D018450:Disease Progression; D005453:Fluorescence; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007382:Intermediate Filaments / Q000378:metabolism*; D051379:Mice; D055806:Microvessels / Q000473:pathology; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000378:metabolism; D012509:Sarcoma / Q000097:blood / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors; D059016:Tumor Microenvironment; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D015820:Cadherins; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D019014:fas Receptor