• Molecular Cancer Biology Program
• Center of Excellence in Cancer Biology
• HBGP - Helsinki Biomedical Graduate Program
• GPBM -
  Helsinki Graduate Program in Biotechnology and Molecular Biology

Contact Information:

Jorma Keski-Oja
M.D., Ph.D., Professor
Molecular Cancer Biology Program
Biomedicum Helsinki
Haartman Institute

PO BOX 63 (Haartmaninkatu 3)
FI-00014 University of Helsinki
Finland

Tel. +358 9 191 25566
Fax. +358 9 191 25610

e-mail :
firstname.surname@helsinki.fi

Secretary Merja Koivulahti

Translational Cancer Biology Researc Program's website has moved.

http://research.med.helsinki.fi/cancerbio/index.html

TGF-ß:s are multifunctional growth and differentiation modulators that are secreted from cells mainly as latent forms. Their expression can be regulated by hormones, retinoids and vitamin D3. Latent TGF-ßs can be activated for example by physicochemical treatments and enzymatically by proteases like plasmin. We found that TGF-ß associates with pericellular structures as a complex of its propeptide and binding proteins, LTBPs. Numerous proteases release matrix-associated TGF-ß, but mainly in the latent form. Our ongoing studies are designed to explore factors that affect the expression of TGF-ß:s, matrix deposition, and the roles of proteases in their release and activation. The matrix and TGF-ß binding domains of the binding protein LTBP have been mapped. The molecular basis for complex formation between LAP and LTBPs has been characterized. We characterize two LTBPs, hLTBPs-3 and -4, and the splicing of the short and long forms of LTBP-1. The work involves analyses on LTBP-ECM protein interactions and proteolytic release as an approach to understand the roles of LTBPs in the storage and focal activation of TGF- ßs.

The research on gelatinase A activation involves analyses of complex formation at the fibrosarcoma and fibroblast cell surfaces. MT1-MMP serves as a capturing and processing molecule for gelatinase A and TIMP-2. The interaction results under suitable conditions to proteolytic processing and release of gelatinase A. The release is accompanied by proteolytic digestion of MT1-MMP to an inactive cell associated 43-kda fragment that lacks the catalytic site. The activation event is finely tuned and can be prevented by an excess of TIMP. Perturbations of the balance in malignant cells can result in excessive activation leading to focal matrix degradation, which is needed in invasive processes.

Page updated December 2, 2014

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