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Palladin expression is a conserved characteristic of the desmoplastic tumor microenvironment and contributes to altered gene expression
Author(s) -
Can Austin R.,
Owen Meredith K.,
Guerrero Michael S.,
Kerber Michael L.,
Goicoechea Silvia M.,
Hemstreet Kathryn C.,
Klazynski Brian,
Hollyfield Johnathan,
Chang Emily H.,
Hwang Rosa F.,
Otey Carol A.,
Kim Hong Jin
Publication year - 2015
Publication title -
cytoskeleton
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.95
H-Index - 86
eISSN - 1949-3592
pISSN - 1949-3584
DOI - 10.1002/cm.21239
Subject(s) - biology , stroma , extracellular matrix , immunohistochemistry , gene isoform , pathology , tumor microenvironment , pancreas , microbiology and biotechnology , gene , cancer , endocrinology , immunology , genetics , medicine
The stroma surrounding solid tumors contributes in complex ways to tumor progression. Cancer‐associated fibroblasts (CAFs) are the predominant cell type in the tumor stroma. Previous studies have shown that the actin‐binding protein palladin is highly expressed in the stroma of pancreas tumors, but the interpretation of these results is complicated by the fact that palladin exists as multiple isoforms. In the current study, the expression and localization of palladin isoform 4 was examined in normal specimens and adenocarcinomas of human pancreas, lung, colon, and stomach samples. Immunohistochemistry with isoform‐selective antibodies revealed that expression of palladin isoform 4 was higher in adenocarcinomas versus normal tissues, and highest in CAFs. Immunohistochemistry staining revealed that palladin was present in both the cytoplasm and the nucleus of CAFs, and this was confirmed using immunofluorescence staining and subcellular fractionation of a pancreatic CAF cell line. To investigate the functional significance of nuclear palladin, RNA Seq analysis of palladin knockdown CAFs versus control CAFs was performed, and the results showed that palladin regulates the expression of genes involved in the biosynthesis and assembly of collagen, and organization of the extracellular matrix. These results suggested that palladin isoform 4 may play a conserved role in establishing the phenotype of CAFs in multiple tumor types. © 2015 Wiley Periodicals, Inc.