Coexpression of vimentin and keratins by human melanoma tumor cells: Correlation with invasive and metastatic potential

Mary J C Hendrix, Elisabeth A. Seftor, Yi Wen Chu, Richard E B Seftor, Raymond B Nagle, Kathleen M. McDaniel, Stanley P L Leong, Karin H. Yohem, Albert M. Leibovitz, Frank L. Meyskens, Dale H. Conaway, Danny R. Welch, Lance A. Liotta, William Stetler-Stevenson

Research output: Contribution to journalArticle

152 Citations (Scopus)

Abstract

Background: Several protein markers, including vimentin, have been used to diagnose human melanoma. Because melanoma often has metastasized by the time of diagnosis, early markers prognostic for metastatic potential need to be identified. Commonly, vimentin is found in mesenchymal cells, and keratins are present in epithelial cells, but recent studies report coexpression of vimentin and keratin(s) in epithelial and nonepithelial neoplasms, including some melanomas. Purpose: Our purpose was to determine whether Coexpression of vimentin and keratin(s) is correlated with tumor cell invasion and metastatic behavior. Methods: We evaluated nine human melanoma cell lines expressing vimentin and other markers of aggressive tumor behavior (HMB-45, S-100, HLA-ABC class I and HLA-DR class II histocompatibility antigens, and K8 and K18 keratins). Levels of K8 and K18 keratins were determined in the highly metastatic C8161 cell line, the poorly metastatic A375P line, and the moderately metastatic A375M line. To determine whether the presence of keratin affects migratory ability, we altered the conformational structure of keratin filaments in C8161 cells by transfection with a mutant K18 complementary DNA. We also determined messenger RNA levels of human type IV collagenase, an enzyme marker for invasion and metastasis. Results: In A375P cells, two-dimensional electrophoresis with Coomassie-stained gels, immunoblotting, and immunofluorescence staining showed no detectable levels of K8 or K18. A375M cells showed low levels of K8 and K18 by Western and Northern blotting, with a distinctive fluorescent subpopulation of cells. In comparison, K8 and K18 levels in C8161 cells were high in all cells. Type IV collagenase messenger RNA levels were lowest in A375P cells and highest in C8161 cells, correlating with invasive ability in vitro and metastatic potential in athymic nude mice. The transfectant clones C1070-10 and C1070-14 derived from the C8161 parent line showed dramatic morphological changes, disrupted keratin Filaments, and decreased invasive and metastatic potential directly correlated with a reduction in migratory activity. Conclusion: These findings show a correlation between the coexpression of vimentin with K8 and K18 keratins and the invasive and metastatic behavior of three representative human melanoma cell lines.

Original languageEnglish (US)
Pages (from-to)165-174
Number of pages10
JournalJournal of the National Cancer Institute
Volume84
Issue number3
StatePublished - Feb 5 1992

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Keratin
Melanoma
Vimentin
Keratins
Tumors
Tumor
Cells
Cell
Neoplasms
Line
Aptitude
Collagenases
Nude Mice
Cell Line
Invasion
Filament
Human
Messenger RNA
Histocompatibility
Glandular and Epithelial Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Radiology Nuclear Medicine and imaging

Cite this

Hendrix, M. J. C., Seftor, E. A., Chu, Y. W., Seftor, R. E. B., Nagle, R. B., McDaniel, K. M., ... Stetler-Stevenson, W. (1992). Coexpression of vimentin and keratins by human melanoma tumor cells: Correlation with invasive and metastatic potential. Journal of the National Cancer Institute, 84(3), 165-174.

Coexpression of vimentin and keratins by human melanoma tumor cells : Correlation with invasive and metastatic potential. / Hendrix, Mary J C; Seftor, Elisabeth A.; Chu, Yi Wen; Seftor, Richard E B; Nagle, Raymond B; McDaniel, Kathleen M.; Leong, Stanley P L; Yohem, Karin H.; Leibovitz, Albert M.; Meyskens, Frank L.; Conaway, Dale H.; Welch, Danny R.; Liotta, Lance A.; Stetler-Stevenson, William.

In: Journal of the National Cancer Institute, Vol. 84, No. 3, 05.02.1992, p. 165-174.

Research output: Contribution to journalArticle

Hendrix, MJC, Seftor, EA, Chu, YW, Seftor, REB, Nagle, RB, McDaniel, KM, Leong, SPL, Yohem, KH, Leibovitz, AM, Meyskens, FL, Conaway, DH, Welch, DR, Liotta, LA & Stetler-Stevenson, W 1992, 'Coexpression of vimentin and keratins by human melanoma tumor cells: Correlation with invasive and metastatic potential', Journal of the National Cancer Institute, vol. 84, no. 3, pp. 165-174.
Hendrix, Mary J C ; Seftor, Elisabeth A. ; Chu, Yi Wen ; Seftor, Richard E B ; Nagle, Raymond B ; McDaniel, Kathleen M. ; Leong, Stanley P L ; Yohem, Karin H. ; Leibovitz, Albert M. ; Meyskens, Frank L. ; Conaway, Dale H. ; Welch, Danny R. ; Liotta, Lance A. ; Stetler-Stevenson, William. / Coexpression of vimentin and keratins by human melanoma tumor cells : Correlation with invasive and metastatic potential. In: Journal of the National Cancer Institute. 1992 ; Vol. 84, No. 3. pp. 165-174.
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title = "Coexpression of vimentin and keratins by human melanoma tumor cells: Correlation with invasive and metastatic potential",
abstract = "Background: Several protein markers, including vimentin, have been used to diagnose human melanoma. Because melanoma often has metastasized by the time of diagnosis, early markers prognostic for metastatic potential need to be identified. Commonly, vimentin is found in mesenchymal cells, and keratins are present in epithelial cells, but recent studies report coexpression of vimentin and keratin(s) in epithelial and nonepithelial neoplasms, including some melanomas. Purpose: Our purpose was to determine whether Coexpression of vimentin and keratin(s) is correlated with tumor cell invasion and metastatic behavior. Methods: We evaluated nine human melanoma cell lines expressing vimentin and other markers of aggressive tumor behavior (HMB-45, S-100, HLA-ABC class I and HLA-DR class II histocompatibility antigens, and K8 and K18 keratins). Levels of K8 and K18 keratins were determined in the highly metastatic C8161 cell line, the poorly metastatic A375P line, and the moderately metastatic A375M line. To determine whether the presence of keratin affects migratory ability, we altered the conformational structure of keratin filaments in C8161 cells by transfection with a mutant K18 complementary DNA. We also determined messenger RNA levels of human type IV collagenase, an enzyme marker for invasion and metastasis. Results: In A375P cells, two-dimensional electrophoresis with Coomassie-stained gels, immunoblotting, and immunofluorescence staining showed no detectable levels of K8 or K18. A375M cells showed low levels of K8 and K18 by Western and Northern blotting, with a distinctive fluorescent subpopulation of cells. In comparison, K8 and K18 levels in C8161 cells were high in all cells. Type IV collagenase messenger RNA levels were lowest in A375P cells and highest in C8161 cells, correlating with invasive ability in vitro and metastatic potential in athymic nude mice. The transfectant clones C1070-10 and C1070-14 derived from the C8161 parent line showed dramatic morphological changes, disrupted keratin Filaments, and decreased invasive and metastatic potential directly correlated with a reduction in migratory activity. Conclusion: These findings show a correlation between the coexpression of vimentin with K8 and K18 keratins and the invasive and metastatic behavior of three representative human melanoma cell lines.",
author = "Hendrix, {Mary J C} and Seftor, {Elisabeth A.} and Chu, {Yi Wen} and Seftor, {Richard E B} and Nagle, {Raymond B} and McDaniel, {Kathleen M.} and Leong, {Stanley P L} and Yohem, {Karin H.} and Leibovitz, {Albert M.} and Meyskens, {Frank L.} and Conaway, {Dale H.} and Welch, {Danny R.} and Liotta, {Lance A.} and William Stetler-Stevenson",
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T1 - Coexpression of vimentin and keratins by human melanoma tumor cells

T2 - Correlation with invasive and metastatic potential

AU - Hendrix, Mary J C

AU - Seftor, Elisabeth A.

AU - Chu, Yi Wen

AU - Seftor, Richard E B

AU - Nagle, Raymond B

AU - McDaniel, Kathleen M.

AU - Leong, Stanley P L

AU - Yohem, Karin H.

AU - Leibovitz, Albert M.

AU - Meyskens, Frank L.

AU - Conaway, Dale H.

AU - Welch, Danny R.

AU - Liotta, Lance A.

AU - Stetler-Stevenson, William

PY - 1992/2/5

Y1 - 1992/2/5

N2 - Background: Several protein markers, including vimentin, have been used to diagnose human melanoma. Because melanoma often has metastasized by the time of diagnosis, early markers prognostic for metastatic potential need to be identified. Commonly, vimentin is found in mesenchymal cells, and keratins are present in epithelial cells, but recent studies report coexpression of vimentin and keratin(s) in epithelial and nonepithelial neoplasms, including some melanomas. Purpose: Our purpose was to determine whether Coexpression of vimentin and keratin(s) is correlated with tumor cell invasion and metastatic behavior. Methods: We evaluated nine human melanoma cell lines expressing vimentin and other markers of aggressive tumor behavior (HMB-45, S-100, HLA-ABC class I and HLA-DR class II histocompatibility antigens, and K8 and K18 keratins). Levels of K8 and K18 keratins were determined in the highly metastatic C8161 cell line, the poorly metastatic A375P line, and the moderately metastatic A375M line. To determine whether the presence of keratin affects migratory ability, we altered the conformational structure of keratin filaments in C8161 cells by transfection with a mutant K18 complementary DNA. We also determined messenger RNA levels of human type IV collagenase, an enzyme marker for invasion and metastasis. Results: In A375P cells, two-dimensional electrophoresis with Coomassie-stained gels, immunoblotting, and immunofluorescence staining showed no detectable levels of K8 or K18. A375M cells showed low levels of K8 and K18 by Western and Northern blotting, with a distinctive fluorescent subpopulation of cells. In comparison, K8 and K18 levels in C8161 cells were high in all cells. Type IV collagenase messenger RNA levels were lowest in A375P cells and highest in C8161 cells, correlating with invasive ability in vitro and metastatic potential in athymic nude mice. The transfectant clones C1070-10 and C1070-14 derived from the C8161 parent line showed dramatic morphological changes, disrupted keratin Filaments, and decreased invasive and metastatic potential directly correlated with a reduction in migratory activity. Conclusion: These findings show a correlation between the coexpression of vimentin with K8 and K18 keratins and the invasive and metastatic behavior of three representative human melanoma cell lines.

AB - Background: Several protein markers, including vimentin, have been used to diagnose human melanoma. Because melanoma often has metastasized by the time of diagnosis, early markers prognostic for metastatic potential need to be identified. Commonly, vimentin is found in mesenchymal cells, and keratins are present in epithelial cells, but recent studies report coexpression of vimentin and keratin(s) in epithelial and nonepithelial neoplasms, including some melanomas. Purpose: Our purpose was to determine whether Coexpression of vimentin and keratin(s) is correlated with tumor cell invasion and metastatic behavior. Methods: We evaluated nine human melanoma cell lines expressing vimentin and other markers of aggressive tumor behavior (HMB-45, S-100, HLA-ABC class I and HLA-DR class II histocompatibility antigens, and K8 and K18 keratins). Levels of K8 and K18 keratins were determined in the highly metastatic C8161 cell line, the poorly metastatic A375P line, and the moderately metastatic A375M line. To determine whether the presence of keratin affects migratory ability, we altered the conformational structure of keratin filaments in C8161 cells by transfection with a mutant K18 complementary DNA. We also determined messenger RNA levels of human type IV collagenase, an enzyme marker for invasion and metastasis. Results: In A375P cells, two-dimensional electrophoresis with Coomassie-stained gels, immunoblotting, and immunofluorescence staining showed no detectable levels of K8 or K18. A375M cells showed low levels of K8 and K18 by Western and Northern blotting, with a distinctive fluorescent subpopulation of cells. In comparison, K8 and K18 levels in C8161 cells were high in all cells. Type IV collagenase messenger RNA levels were lowest in A375P cells and highest in C8161 cells, correlating with invasive ability in vitro and metastatic potential in athymic nude mice. The transfectant clones C1070-10 and C1070-14 derived from the C8161 parent line showed dramatic morphological changes, disrupted keratin Filaments, and decreased invasive and metastatic potential directly correlated with a reduction in migratory activity. Conclusion: These findings show a correlation between the coexpression of vimentin with K8 and K18 keratins and the invasive and metastatic behavior of three representative human melanoma cell lines.

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