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Activation of fibroblast collagenase-1 expression by tumor cells of squamous cell carcinomas is mediated by p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase-2.
Cancer Res 2000; 60(24):7156-62CR

Abstract

Collagenase-1 [matrix metalloproteinase (MMP)-1] is expressed by stromal fibroblasts of various invasive malignant tumors. Here, we have examined the molecular mechanisms of tumor-induced expression of MMP-1 by stromal fibroblasts. Treatment of fibroblasts with conditioned media of tumor cells derived from squamous cell carcinomas (SCCs) of the oral cavity and larynx resulted in activation of fibroblast MMP-1 expression at the transcriptional level. The induction of MMP-1 expression correlates with activation of c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase and phosphorylation of c-Jun and activating transcription factor-2 (ATF-2) and is dependent on the activity of p38 mitogen-activated protein kinase. Furthermore, using fibroblasts derived from JNK2-/- mice, we show that JNK2 is required for induction of fibroblast collagenase-3 expression in response to conditioned SCC tumor cell medium. Together, these results provide evidence that stress-activated p38 and JNK pathways play a crucial role in paracrine regulation of collagenolytic capacity of stromal fibroblasts in SCCs and suggest JNK2 as a novel target for inhibition of MMP-1 expression and tumor invasion.

Authors+Show Affiliations

Turku Centre for Biotechnology, University of Turku, Finland. jukwes@utu.fiNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11156425

Citation

Westermarck, J, et al. "Activation of Fibroblast Collagenase-1 Expression By Tumor Cells of Squamous Cell Carcinomas Is Mediated By P38 Mitogen-activated Protein Kinase and c-Jun NH2-terminal Kinase-2." Cancer Research, vol. 60, no. 24, 2000, pp. 7156-62.
Westermarck J, Li S, Jaakkola P, et al. Activation of fibroblast collagenase-1 expression by tumor cells of squamous cell carcinomas is mediated by p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase-2. Cancer Res. 2000;60(24):7156-62.
Westermarck, J., Li, S., Jaakkola, P., Kallunki, T., Grénman, R., & Kähäri, V. M. (2000). Activation of fibroblast collagenase-1 expression by tumor cells of squamous cell carcinomas is mediated by p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase-2. Cancer Research, 60(24), pp. 7156-62.
Westermarck J, et al. Activation of Fibroblast Collagenase-1 Expression By Tumor Cells of Squamous Cell Carcinomas Is Mediated By P38 Mitogen-activated Protein Kinase and c-Jun NH2-terminal Kinase-2. Cancer Res. 2000 Dec 15;60(24):7156-62. PubMed PMID: 11156425.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of fibroblast collagenase-1 expression by tumor cells of squamous cell carcinomas is mediated by p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase-2. AU - Westermarck,J, AU - Li,S, AU - Jaakkola,P, AU - Kallunki,T, AU - Grénman,R, AU - Kähäri,V M, PY - 2001/1/13/pubmed PY - 2001/3/3/medline PY - 2001/1/13/entrez SP - 7156 EP - 62 JF - Cancer research JO - Cancer Res. VL - 60 IS - 24 N2 - Collagenase-1 [matrix metalloproteinase (MMP)-1] is expressed by stromal fibroblasts of various invasive malignant tumors. Here, we have examined the molecular mechanisms of tumor-induced expression of MMP-1 by stromal fibroblasts. Treatment of fibroblasts with conditioned media of tumor cells derived from squamous cell carcinomas (SCCs) of the oral cavity and larynx resulted in activation of fibroblast MMP-1 expression at the transcriptional level. The induction of MMP-1 expression correlates with activation of c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase and phosphorylation of c-Jun and activating transcription factor-2 (ATF-2) and is dependent on the activity of p38 mitogen-activated protein kinase. Furthermore, using fibroblasts derived from JNK2-/- mice, we show that JNK2 is required for induction of fibroblast collagenase-3 expression in response to conditioned SCC tumor cell medium. Together, these results provide evidence that stress-activated p38 and JNK pathways play a crucial role in paracrine regulation of collagenolytic capacity of stromal fibroblasts in SCCs and suggest JNK2 as a novel target for inhibition of MMP-1 expression and tumor invasion. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/11156425/Activation_of_fibroblast_collagenase_1_expression_by_tumor_cells_of_squamous_cell_carcinomas_is_mediated_by_p38_mitogen_activated_protein_kinase_and_c_Jun_NH2_terminal_kinase_2_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11156425 DB - PRIME DP - Unbound Medicine ER -