Isoform-specific upregulation of palladin in human and murine pancreas tumors

Silvia M. Goicoechea, Brian Bednarski, Christianna Stack, David W. Cowan, Keith Volmar, Leigh Thorne, Edna Cukierman, Anil K. Rustgi, Teresa Brentnall, Rosa F. Hwang, Christopher A.G. McCulloch, Jen Jen Yeh, David J. Bentrem, Steven N. Hochwald, Sunil R. Hingorani, Hong Jin Kim, Carol A. Otey

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Pancreatic ductal adenocarcinoma (PDA) is a lethal disease with a characteristic pattern of early metastasis, which is driving a search for biomarkers that can be used to detect the cancer at an early stage. Recently, the actin-associated protein palladin was identified as a candidate biomarker when it was shown that palladin is mutated in a rare inherited form of PDA, and overexpressed in many sporadic pancreas tumors and premalignant precursors. In this study, we analyzed the expression of palladin isoforms in murine and human PDA and explored palladin's potential use in diagnosing PDA. We performed immunohistochemistry and immunoblot analyses on patient samples and tumor-derived cells using an isoformselective monoclonal antibody and a pan-palladin polyclonal antibody. Immunoblot and real-time quantitative reverse transcription-PCR were used to quantify palladin mRNA levels in human samples. We show that there are two major paladin isoforms expressed in pancreas: 65 and 85-90 kDa. The 65 kDa isoform is expressed in both normal and neoplastic ductal epithelial cells. The 85-90 kDa palladin isoform is highly overexpressed in tumor-associated fibroblasts (TAFs) in both primary and metastatic tumors compared to normal pancreas, in samples obtained from either human patients or genetically engineered mice. In tumor-derived cultured cells, expression of palladin isoforms follows cell-type specific patterns, with the 85-90 kDa isoform in TAFs, and the 65 kDa isoform predominating in normal and neoplastic epithelial cells. These results suggest that upregulation of 85-90 kDa palladin isoform may play a role in the establishment of the TAF phenotype, and thus in the formation of a desmoplastic tumor microenvironment. Thus, palladin may have a potential use in the early diagnosis of PDA and may have much broader significance in understanding metastatic behavior.

Original languageEnglish (US)
Article numbere10347
JournalPloS one
Volume5
Issue number4
DOIs
StatePublished - Sep 14 2010

Fingerprint

pancreas
Tumors
Pancreas
Protein Isoforms
Up-Regulation
neoplasms
adenocarcinoma
mice
Adenocarcinoma
Neoplasms
Fibroblasts
fibroblasts
Biomarkers
Epithelial Cells
biomarkers
epithelial cells
Cultured Tumor Cells
Tumor Microenvironment
Transcription
early diagnosis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Goicoechea, S. M., Bednarski, B., Stack, C., Cowan, D. W., Volmar, K., Thorne, L., ... Otey, C. A. (2010). Isoform-specific upregulation of palladin in human and murine pancreas tumors. PloS one, 5(4), [e10347]. https://doi.org/10.1371/journal.pone.0010347
Goicoechea, Silvia M. ; Bednarski, Brian ; Stack, Christianna ; Cowan, David W. ; Volmar, Keith ; Thorne, Leigh ; Cukierman, Edna ; Rustgi, Anil K. ; Brentnall, Teresa ; Hwang, Rosa F. ; McCulloch, Christopher A.G. ; Yeh, Jen Jen ; Bentrem, David J. ; Hochwald, Steven N. ; Hingorani, Sunil R. ; Kim, Hong Jin ; Otey, Carol A. / Isoform-specific upregulation of palladin in human and murine pancreas tumors. In: PloS one. 2010 ; Vol. 5, No. 4.
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abstract = "Pancreatic ductal adenocarcinoma (PDA) is a lethal disease with a characteristic pattern of early metastasis, which is driving a search for biomarkers that can be used to detect the cancer at an early stage. Recently, the actin-associated protein palladin was identified as a candidate biomarker when it was shown that palladin is mutated in a rare inherited form of PDA, and overexpressed in many sporadic pancreas tumors and premalignant precursors. In this study, we analyzed the expression of palladin isoforms in murine and human PDA and explored palladin's potential use in diagnosing PDA. We performed immunohistochemistry and immunoblot analyses on patient samples and tumor-derived cells using an isoformselective monoclonal antibody and a pan-palladin polyclonal antibody. Immunoblot and real-time quantitative reverse transcription-PCR were used to quantify palladin mRNA levels in human samples. We show that there are two major paladin isoforms expressed in pancreas: 65 and 85-90 kDa. The 65 kDa isoform is expressed in both normal and neoplastic ductal epithelial cells. The 85-90 kDa palladin isoform is highly overexpressed in tumor-associated fibroblasts (TAFs) in both primary and metastatic tumors compared to normal pancreas, in samples obtained from either human patients or genetically engineered mice. In tumor-derived cultured cells, expression of palladin isoforms follows cell-type specific patterns, with the 85-90 kDa isoform in TAFs, and the 65 kDa isoform predominating in normal and neoplastic epithelial cells. These results suggest that upregulation of 85-90 kDa palladin isoform may play a role in the establishment of the TAF phenotype, and thus in the formation of a desmoplastic tumor microenvironment. Thus, palladin may have a potential use in the early diagnosis of PDA and may have much broader significance in understanding metastatic behavior.",
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Goicoechea, SM, Bednarski, B, Stack, C, Cowan, DW, Volmar, K, Thorne, L, Cukierman, E, Rustgi, AK, Brentnall, T, Hwang, RF, McCulloch, CAG, Yeh, JJ, Bentrem, DJ, Hochwald, SN, Hingorani, SR, Kim, HJ & Otey, CA 2010, 'Isoform-specific upregulation of palladin in human and murine pancreas tumors', PloS one, vol. 5, no. 4, e10347. https://doi.org/10.1371/journal.pone.0010347

Isoform-specific upregulation of palladin in human and murine pancreas tumors. / Goicoechea, Silvia M.; Bednarski, Brian; Stack, Christianna; Cowan, David W.; Volmar, Keith; Thorne, Leigh; Cukierman, Edna; Rustgi, Anil K.; Brentnall, Teresa; Hwang, Rosa F.; McCulloch, Christopher A.G.; Yeh, Jen Jen; Bentrem, David J.; Hochwald, Steven N.; Hingorani, Sunil R.; Kim, Hong Jin; Otey, Carol A.

In: PloS one, Vol. 5, No. 4, e10347, 14.09.2010.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Isoform-specific upregulation of palladin in human and murine pancreas tumors

AU - Goicoechea, Silvia M.

AU - Bednarski, Brian

AU - Stack, Christianna

AU - Cowan, David W.

AU - Volmar, Keith

AU - Thorne, Leigh

AU - Cukierman, Edna

AU - Rustgi, Anil K.

AU - Brentnall, Teresa

AU - Hwang, Rosa F.

AU - McCulloch, Christopher A.G.

AU - Yeh, Jen Jen

AU - Bentrem, David J.

AU - Hochwald, Steven N.

AU - Hingorani, Sunil R.

AU - Kim, Hong Jin

AU - Otey, Carol A.

PY - 2010/9/14

Y1 - 2010/9/14

N2 - Pancreatic ductal adenocarcinoma (PDA) is a lethal disease with a characteristic pattern of early metastasis, which is driving a search for biomarkers that can be used to detect the cancer at an early stage. Recently, the actin-associated protein palladin was identified as a candidate biomarker when it was shown that palladin is mutated in a rare inherited form of PDA, and overexpressed in many sporadic pancreas tumors and premalignant precursors. In this study, we analyzed the expression of palladin isoforms in murine and human PDA and explored palladin's potential use in diagnosing PDA. We performed immunohistochemistry and immunoblot analyses on patient samples and tumor-derived cells using an isoformselective monoclonal antibody and a pan-palladin polyclonal antibody. Immunoblot and real-time quantitative reverse transcription-PCR were used to quantify palladin mRNA levels in human samples. We show that there are two major paladin isoforms expressed in pancreas: 65 and 85-90 kDa. The 65 kDa isoform is expressed in both normal and neoplastic ductal epithelial cells. The 85-90 kDa palladin isoform is highly overexpressed in tumor-associated fibroblasts (TAFs) in both primary and metastatic tumors compared to normal pancreas, in samples obtained from either human patients or genetically engineered mice. In tumor-derived cultured cells, expression of palladin isoforms follows cell-type specific patterns, with the 85-90 kDa isoform in TAFs, and the 65 kDa isoform predominating in normal and neoplastic epithelial cells. These results suggest that upregulation of 85-90 kDa palladin isoform may play a role in the establishment of the TAF phenotype, and thus in the formation of a desmoplastic tumor microenvironment. Thus, palladin may have a potential use in the early diagnosis of PDA and may have much broader significance in understanding metastatic behavior.

AB - Pancreatic ductal adenocarcinoma (PDA) is a lethal disease with a characteristic pattern of early metastasis, which is driving a search for biomarkers that can be used to detect the cancer at an early stage. Recently, the actin-associated protein palladin was identified as a candidate biomarker when it was shown that palladin is mutated in a rare inherited form of PDA, and overexpressed in many sporadic pancreas tumors and premalignant precursors. In this study, we analyzed the expression of palladin isoforms in murine and human PDA and explored palladin's potential use in diagnosing PDA. We performed immunohistochemistry and immunoblot analyses on patient samples and tumor-derived cells using an isoformselective monoclonal antibody and a pan-palladin polyclonal antibody. Immunoblot and real-time quantitative reverse transcription-PCR were used to quantify palladin mRNA levels in human samples. We show that there are two major paladin isoforms expressed in pancreas: 65 and 85-90 kDa. The 65 kDa isoform is expressed in both normal and neoplastic ductal epithelial cells. The 85-90 kDa palladin isoform is highly overexpressed in tumor-associated fibroblasts (TAFs) in both primary and metastatic tumors compared to normal pancreas, in samples obtained from either human patients or genetically engineered mice. In tumor-derived cultured cells, expression of palladin isoforms follows cell-type specific patterns, with the 85-90 kDa isoform in TAFs, and the 65 kDa isoform predominating in normal and neoplastic epithelial cells. These results suggest that upregulation of 85-90 kDa palladin isoform may play a role in the establishment of the TAF phenotype, and thus in the formation of a desmoplastic tumor microenvironment. Thus, palladin may have a potential use in the early diagnosis of PDA and may have much broader significance in understanding metastatic behavior.

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Goicoechea SM, Bednarski B, Stack C, Cowan DW, Volmar K, Thorne L et al. Isoform-specific upregulation of palladin in human and murine pancreas tumors. PloS one. 2010 Sep 14;5(4). e10347. https://doi.org/10.1371/journal.pone.0010347