Studies of Mesenchymal Progenitor Cells and Tumour Growth, Integrins and Matrix Metalloproteinases

Abstract

In this thesis we characterize the effect of mesenchymal progenitor cells (MPCs) on tumour growth, and show that MPCs can have inhibitory effects on tumour development. We developed a method to subcutaneously transplant tumour cells, cultured in vitro in a pre-formed gelatin matrix, that made it possible to study the early phases of tumour development. Using this method we inoculated rats with gelatine matrices containing MPCs mixed with colon carcinoma cells. We found that, in the presence of MPCs, the early tumour development was inhibited and we could demonstrate an altered pattern of infiltrating cells. This inhibitory effect was confirmed and further studied using intra-hepatic and retro-peritoneal co-injections of colon carcinoma cells and MPCs. Supporting this finding we demonstate, using a glioma tumour model, that subcutaneous or intra-cranial co-injections of MPCs and tumour cells, results in retarded tumour growth. Furthermore, we show an inhibitory effect from MPCs on the proliferation of both tumour cells and SEA stimulated lymphocytes in vitro.



We also studied the interaction between the collagen-binding integrins ?10?1 and ?11?1 and the collagen degrading enzyme matrix metalloproteinase-13 (MMP-13). Using the ?10 and ?11 I-domains, as well as solubilised integrins we found that proMMP-13, but not proMMP-9, bound in a cation independent manner and that the binding was abrogated when the pro-enzyme was activated. We also found that pre-incubation of the ?10 and ?11 I-domains with a triple helical collagen peptide increased the capacity of the integrins to bind proMMP-13. Taken together, this implicates the collagen-binding integrins ?10?1 and ?11?1 as important targets in the control of MMP activity in pathological conditions such as tumour invasion and metastasis and cartilage degeneration in arthritic disease.

• author: Bryngelsson Ohlsson, Lars
• supervisor: Evy Lundgren-Åkerlund
• opponent: Professor Johansson, Staffan, Uppsala University, Dep. of medical biochemistry and microbiology
• organization: Immunology (research group)
• publishing date: 2005
• type: Thesis
• publication status: published
• subject: Basic Medicine
• keywords: Immunology, Tumour inhibition, cancer, onkologi, cancerology, Cytologi, oncology, Cytology, Biologi, Biology, Medicin (människa och djur), Medicine (human and vertebrates), Integrin matrix metalloproteinase interaction, Immunologi, serologi, transplantation, Proteins, enzymology, Proteiner, enzymologi, serology, Mesenchumal progenitor cells
• pages: 122 pages
• defense location: GK-salen BMC Sölvegatan 19 221 84 Lund
• defense date: 2005-11-11 13:00:00
• ISBN: 91-85439-98-3
• language: English
• LU publication?: yes
• additional info: Lars Bryngelson Ohlsson, Laura Varas, Christian Kjellman, Klaus Edvardsen and Magnus Lindvall. 2003. Mesenchymal progenitor cell-mediated inhibition of tumor growth in vivo and in vitro in gelatin matrix. Experimental and Molecular Pathology, vol 75 pp 248-255.; Laura Varas, Lars Bryngelson Ohlsson, Christian Kjellman, Klaus Edvardsen, Hans-Olov Sjögren, Johan Richter and Magnus Lindvall. . Rat mesenchymal progenitor cells inhibit tumor growth in vivo and tumor proliferation in vitro. (manuscript); Lars Bryngelson Ohlsson, Mark Hickery, Rikard Holmdahl, Christian Kjellman and Evy Lundgren-Åkerlund. . The collagen-binding integrins alpha10beta1 and alpha11beta1 interact with proMMP-13. A collagen peptide regulates the I-domain/MMP-13 interaction. (manuscript) The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Department of Experimental Medical Science (013210000), Medical Inflammation Research (013212019)
• id: 88f1c6bf-ad86-4f9b-a7d6-1e6a86a308e9 (old id 545545)
• date added to LUP: 2016-04-01 15:25:56
• date last changed: 2018-11-21 20:34:25