In this project, our specific aim is to characterize molecular mechanisms regulating deposition and turnover of extracellular matrix. We examine the role and regulation of matrix metalloproteinases (MMPs), as well as their specific inhibitors, TIMPs, in tumor growth and invasion, tissue repair, and fibrosis. We are specifically interested in elucidating the signaling mechanisms regulating the expression of MMPs in the invasion and migration of normal and malignant cells. We want to evaluate specific MMPs as diagnostic markers for metastases of malignant tumors and as prognostic indicators for metastasis capacity of highly invasive primary tumors. Understanding the mechanisms regulating proteolytic capacity of normal and malignant cells is important in development of specific therapeutic modalities for preventing tumor growth and metastasis, and may also be utilized in developing treatment for defective tissue repair, as well as for disorders involving excessive degradation of connective tissue, e.g. rheumatoid arthritis and osteoarthritis. Dr .Kahari is a senior scientist at the Centre for Biotechnology of the University of Turku. His group currently consists of 8 graduate students and 2 technicians.

See also the group's page on the Center of Biotechnology site

• Regulation of MMP expression
• Role of MMPs in cell migration and invasion
• MMPs and TIMPs in cancer growth and invasion
• MMPs and TIMPs in wound repair and fibrosis
• Regulation of collagen expression

• Westermarck J, Seth A, Kähäri V-M. (1997) Differential regulation of interstitial collagenase (MMP-1) gene expression by ETS transcription factors. Oncogene 14:2651-2660.
  
  PubMed - abstract

• Johansson N, Airola K, Grénman R, Kariniemi A-L, Saarialho-Kere U, Kähäri V-M. (1997) Expression of collagenase-3 (matrix metalloproteinase-13) in squamous cell carcinomas of the head and neck. Am J Pathol 151:499-508.
  
  PubMed - abstract

• Reunanen N, Westermarck J, Häkkinen L, Holmström TH, Elo I, Eriksson JE, Kähäri V-M. (1998) Enhancement of fibroblast collagenase-1 (MMP-1) gene expression by ceramide is mediated by extracellular signal-regulated and stress-activated protein kinase pathways. J Biol Chem 273:5137-5145.
  
  PubMed - abstract

• Ahonen M, Baker AH, Kähäri V-M. (1998) Adenovirus-mediated gene delivery of tissue inhibitor of metalloproteinases-3 inhibits invasion and induces apoptosis in melanoma cells. Cancer Res 58:2310-2315.
  
  PubMed - abstract

• Ravanti L, Heino J, López-Otín C, Kähäri V-M. (1999) Induction of collagenase-3 (MMP-13) expression in human skin fibroblasts by three-dimensional collagen is mediated by p38 mitogen-activated protein kinase. J Biol Chem 74:2446-2455.
  
  PubMed - abstract

• Johansson N, Vaalamo M, Grénman S, Hietanen S, Klemi P, Saarialho-Kere U, Kähäri V-M. (1999) Collagenase-3 (MMP-13) is expressed by tumor cells in invasive vulvar squamous cell carcinomas. Am J Pathol 154:469-478.
  
  PubMed - abstract

• Ravanti L, Häkkinen L, Larjava H, Saarialho-Kere U, Foschi M, Han J, Kähäri V-M. (1999) Transforming growth factor-b induces collagenase-3 expression by human gingival fibroblasts via p38 mitogen-activated protein kinase. J Biol Chem 274:37292-37300.
  
  PubMed - abstract

• Johansson N, Ala-aho R, Uitto V-J, Grénman R, Fusenig NE, López-Otín C, Kähäri V-M. (2000) Expression of collagenase-3 (MMP-13) and collagenase-1 (MMP-1) by transformed keratinocytes is dependent on the activity of p38 mitogen-activated protein kinase. J Cell Sci 113:227-235.
  
  PubMed - abstract

• Ala-aho R, Johansson N, Grénman R, Fusenig NE, López-Otín C, Kähäri V-M. (2000) Inhibition of collagenase-3 (MMP-13) expression in transformed human keratinocytes by interferon-g is associated with activation of extracellular signal-regulated kinase1,2 and STAT1. Oncogene 19:248-257.
  
  PubMed - abstract

• Laine P, Reunanen N, Ravanti L, Foschi M, Santra M, Iozzo RV, Kähäri V-M. (2000) Activation of extracellular signal-regulated kinase1,2 results in down-regulation of decorin expression in fibroblasts. Biochem J 349:19-25.
  
  PubMed - abstract

• Reunanen N, Foschi M, Han J, Kähäri V-M. (2000) Activation of extracellular signal-regulated kinase-1/2 inhibits type I collagen expression in human skin fibroblasts. J Biol Chem 275:34634-34639
  
  PubMed - abstract

• 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 Jun N-terminal kinase-2. Cancer Res (In press)
  
  PubMed - abstract

Doctoral Theses

• Transcriptional regulation of fibroblast collagenase (MMP-1) gene expression. Jukka Westermarck, 1997

• Human collagenase-3 (MMP-13) in development and malignant transformation. Nina Johansson, 1998

• Regulation of the expression of human collagenase-3 (MMP-13) - Implications for wound repair and dermal fibrosis. Laura Ravanti, 2000