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

Bryngelsson Ohlsson, Lars LU (2005)
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Johansson, Staffan, Uppsala University, Dep. of medical biochemistry and microbiology
organization
publishing date
type
Thesis
publication status
published
subject
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
publisher
Department of Experimental Medical Science, Lund Univeristy
defense location
GK-salen BMC Sölvegatan 19 221 84 Lund
defense date
2005-11-11 13:00
ISSN
1652-8220
ISBN
91-85439-98-3
language
English
LU publication?
yes
id
88f1c6bf-ad86-4f9b-a7d6-1e6a86a308e9 (old id 545545)
date added to LUP
2007-09-10 12:38:10
date last changed
2016-09-19 08:44:52
@phdthesis{88f1c6bf-ad86-4f9b-a7d6-1e6a86a308e9,
  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.<br/><br>
<br/><br>
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},
  isbn         = {91-85439-98-3},
  issn         = {1652-8220},
  keyword      = {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},
  language     = {eng},
  pages        = {122},
  publisher    = {Department of Experimental Medical Science, Lund Univeristy},
  school       = {Lund University},
  title        = {Studies of Mesenchymal Progenitor Cells and Tumour Growth, Integrins and Matrix Metalloproteinases},
  year         = {2005},
}