Expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) by colorectal cancer cells and adjacent stroma cells--associations with histopathology and patients outcome

Søren Astrup Jensen; Ben Vainer; Annette Bartels; Nils Brünner; Jens Benn Sørensen

doi:10.1016/j.ejca.2010.07.046

Expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) by colorectal cancer cells and adjacent stroma cells--associations with histopathology and patients outcome

Søren Astrup Jensen, Ben Vainer, Annette Bartels, Nils Brünner, Jens Benn Sørensen

Department of Clinical Medicine

38 Citations (Scopus)

Abstract

Aim: To elucidate cellular features accountable for colorectal cancers' (CRC) capability to invade normal tissue and to metastasize, we investigated the level of the collagenase matrix metalloproteinase 9 (MMP-9) and its physiological inhibitor tissue inhibitor of metalloproteinases 1 (TIMP-1) in cancer cells and supporting stroma cells of CRC. Methods: Immunoreactivity of MMP-9 and TIMP-1 by carcinoma cells, lymphocytes and fibroblasts in archival specimens of paraffin-embedded primary tumours were retrospectively associated with outcome in 340 consecutive patients completely resected for CRC stages II-IV and subsequently treated with adjuvant 5-fluorouracil. Results: Expression of MMP-9 by carcinoma cells was demonstrated in 9% of specimens without association to recurrence free survival (RFS) (HR = 1.0; 95% CI: 0.6-1.8; P = 0.9) or overall survival (OS) (HR = 0.9; 95% CI: 0.5-1.6; P = 0.6). TIMP-1 expression by carcinoma cells, which appeared in 64% of the specimens, was inversely related with RFS (HR = 1.3; 95% CI: 0.9-1.8; P = 0.08) and OS (HR = 1.5; 95% CI: 1.1-2.1; P = 0.02). Expression of TIMP-1 by fibroblasts at the invasive border was directly related to RFS (HR = 0.7; 95% CI: 0.6-0.9; P = 0.02) and OS (HR = 0.7; 95% CI: 0.6-1.0; P = 0.05). Expression of MMP-9 by lymphocytes correlated significantly with the degree of peritumoural inflammation (P = 0.02) but not with RFS (HR = 0.9; 95% CI: 0.7-1.1; P = 0.2) or OS (HR = 0.8; 95% CI: 0.7-1.0; P = 0.07). Conclusion: TIMP-1 in cancer cells is associated with poor prognosis independent of its function as inhibitor of MMP-9. MMP-9 and TIMP-1 are important mediators of the host-cancer cell interaction in the tumour microenvironment with significant influence on the histopathology and on prognosis of CRC.

Original language	English
Journal	European journal of cancer (Oxford, England : 1990)
Volume	46
Issue number	18
Pages (from-to)	3233-42
Number of pages	10
ISSN	0959-8049
DOIs	https://doi.org/10.1016/j.ejca.2010.07.046
Publication status	Published - Dec 2010

Keywords

Adult
Aged
Colorectal Neoplasms
Disease-Free Survival
Female
Humans
Immunohistochemistry
Male
Matrix Metalloproteinase 9
Microscopy, Electron
Middle Aged
Neoplasm Metastasis
Neoplasm Proteins
Prognosis
Stromal Cells
Tissue Inhibitor of Metalloproteinase-1
Tumor Cells, Cultured

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Jensen, S. A., Vainer, B., Bartels, A., Brünner, N., & Sørensen, J. B. (2010). Expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) by colorectal cancer cells and adjacent stroma cells--associations with histopathology and patients outcome. European journal of cancer (Oxford, England : 1990), 46(18), 3233-42. https://doi.org/10.1016/j.ejca.2010.07.046

Expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) by colorectal cancer cells and adjacent stroma cells--associations with histopathology and patients outcome. / Jensen, Søren Astrup; Vainer, Ben; Bartels, Annette et al.
In: European journal of cancer (Oxford, England : 1990), Vol. 46, No. 18, 12.2010, p. 3233-42.

Research output: Contribution to journal › Journal article › Research › peer-review

Jensen, SA, Vainer, B, Bartels, A , Brünner, N & Sørensen, JB 2010, 'Expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) by colorectal cancer cells and adjacent stroma cells--associations with histopathology and patients outcome', European journal of cancer (Oxford, England : 1990), vol. 46, no. 18, pp. 3233-42. https://doi.org/10.1016/j.ejca.2010.07.046

Jensen SA, Vainer B, Bartels A , Brünner N , Sørensen JB. Expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) by colorectal cancer cells and adjacent stroma cells--associations with histopathology and patients outcome. European journal of cancer (Oxford, England : 1990). 2010 Dec;46(18):3233-42. doi: 10.1016/j.ejca.2010.07.046

Jensen, Søren Astrup ; Vainer, Ben ; Bartels, Annette et al. / Expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) by colorectal cancer cells and adjacent stroma cells--associations with histopathology and patients outcome. In: European journal of cancer (Oxford, England : 1990). 2010 ; Vol. 46, No. 18. pp. 3233-42.

@article{f55693e91ad74b18bfbc99697c883810,

title = "Expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) by colorectal cancer cells and adjacent stroma cells--associations with histopathology and patients outcome",

abstract = "Aim: To elucidate cellular features accountable for colorectal cancers' (CRC) capability to invade normal tissue and to metastasize, we investigated the level of the collagenase matrix metalloproteinase 9 (MMP-9) and its physiological inhibitor tissue inhibitor of metalloproteinases 1 (TIMP-1) in cancer cells and supporting stroma cells of CRC. Methods: Immunoreactivity of MMP-9 and TIMP-1 by carcinoma cells, lymphocytes and fibroblasts in archival specimens of paraffin-embedded primary tumours were retrospectively associated with outcome in 340 consecutive patients completely resected for CRC stages II-IV and subsequently treated with adjuvant 5-fluorouracil. Results: Expression of MMP-9 by carcinoma cells was demonstrated in 9% of specimens without association to recurrence free survival (RFS) (HR = 1.0; 95% CI: 0.6-1.8; P = 0.9) or overall survival (OS) (HR = 0.9; 95% CI: 0.5-1.6; P = 0.6). TIMP-1 expression by carcinoma cells, which appeared in 64% of the specimens, was inversely related with RFS (HR = 1.3; 95% CI: 0.9-1.8; P = 0.08) and OS (HR = 1.5; 95% CI: 1.1-2.1; P = 0.02). Expression of TIMP-1 by fibroblasts at the invasive border was directly related to RFS (HR = 0.7; 95% CI: 0.6-0.9; P = 0.02) and OS (HR = 0.7; 95% CI: 0.6-1.0; P = 0.05). Expression of MMP-9 by lymphocytes correlated significantly with the degree of peritumoural inflammation (P = 0.02) but not with RFS (HR = 0.9; 95% CI: 0.7-1.1; P = 0.2) or OS (HR = 0.8; 95% CI: 0.7-1.0; P = 0.07). Conclusion: TIMP-1 in cancer cells is associated with poor prognosis independent of its function as inhibitor of MMP-9. MMP-9 and TIMP-1 are important mediators of the host-cancer cell interaction in the tumour microenvironment with significant influence on the histopathology and on prognosis of CRC.",

keywords = "Adult, Aged, Colorectal Neoplasms, Disease-Free Survival, Female, Humans, Immunohistochemistry, Male, Matrix Metalloproteinase 9, Microscopy, Electron, Middle Aged, Neoplasm Metastasis, Neoplasm Proteins, Prognosis, Stromal Cells, Tissue Inhibitor of Metalloproteinase-1, Tumor Cells, Cultured",

author = "Jensen, {S{\o}ren Astrup} and Ben Vainer and Annette Bartels and Nils Br{\"u}nner and S{\o}rensen, {Jens Benn}",

year = "2010",

month = dec,

doi = "10.1016/j.ejca.2010.07.046",

language = "English",

volume = "46",

pages = "3233--42",

journal = "European journal of cancer (Oxford, England : 1990)",

issn = "0959-8049",

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T1 - Expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) by colorectal cancer cells and adjacent stroma cells--associations with histopathology and patients outcome

AU - Jensen, Søren Astrup

AU - Vainer, Ben

AU - Bartels, Annette

AU - Brünner, Nils

AU - Sørensen, Jens Benn

PY - 2010/12

Y1 - 2010/12

N2 - Aim: To elucidate cellular features accountable for colorectal cancers' (CRC) capability to invade normal tissue and to metastasize, we investigated the level of the collagenase matrix metalloproteinase 9 (MMP-9) and its physiological inhibitor tissue inhibitor of metalloproteinases 1 (TIMP-1) in cancer cells and supporting stroma cells of CRC. Methods: Immunoreactivity of MMP-9 and TIMP-1 by carcinoma cells, lymphocytes and fibroblasts in archival specimens of paraffin-embedded primary tumours were retrospectively associated with outcome in 340 consecutive patients completely resected for CRC stages II-IV and subsequently treated with adjuvant 5-fluorouracil. Results: Expression of MMP-9 by carcinoma cells was demonstrated in 9% of specimens without association to recurrence free survival (RFS) (HR = 1.0; 95% CI: 0.6-1.8; P = 0.9) or overall survival (OS) (HR = 0.9; 95% CI: 0.5-1.6; P = 0.6). TIMP-1 expression by carcinoma cells, which appeared in 64% of the specimens, was inversely related with RFS (HR = 1.3; 95% CI: 0.9-1.8; P = 0.08) and OS (HR = 1.5; 95% CI: 1.1-2.1; P = 0.02). Expression of TIMP-1 by fibroblasts at the invasive border was directly related to RFS (HR = 0.7; 95% CI: 0.6-0.9; P = 0.02) and OS (HR = 0.7; 95% CI: 0.6-1.0; P = 0.05). Expression of MMP-9 by lymphocytes correlated significantly with the degree of peritumoural inflammation (P = 0.02) but not with RFS (HR = 0.9; 95% CI: 0.7-1.1; P = 0.2) or OS (HR = 0.8; 95% CI: 0.7-1.0; P = 0.07). Conclusion: TIMP-1 in cancer cells is associated with poor prognosis independent of its function as inhibitor of MMP-9. MMP-9 and TIMP-1 are important mediators of the host-cancer cell interaction in the tumour microenvironment with significant influence on the histopathology and on prognosis of CRC.

AB - Aim: To elucidate cellular features accountable for colorectal cancers' (CRC) capability to invade normal tissue and to metastasize, we investigated the level of the collagenase matrix metalloproteinase 9 (MMP-9) and its physiological inhibitor tissue inhibitor of metalloproteinases 1 (TIMP-1) in cancer cells and supporting stroma cells of CRC. Methods: Immunoreactivity of MMP-9 and TIMP-1 by carcinoma cells, lymphocytes and fibroblasts in archival specimens of paraffin-embedded primary tumours were retrospectively associated with outcome in 340 consecutive patients completely resected for CRC stages II-IV and subsequently treated with adjuvant 5-fluorouracil. Results: Expression of MMP-9 by carcinoma cells was demonstrated in 9% of specimens without association to recurrence free survival (RFS) (HR = 1.0; 95% CI: 0.6-1.8; P = 0.9) or overall survival (OS) (HR = 0.9; 95% CI: 0.5-1.6; P = 0.6). TIMP-1 expression by carcinoma cells, which appeared in 64% of the specimens, was inversely related with RFS (HR = 1.3; 95% CI: 0.9-1.8; P = 0.08) and OS (HR = 1.5; 95% CI: 1.1-2.1; P = 0.02). Expression of TIMP-1 by fibroblasts at the invasive border was directly related to RFS (HR = 0.7; 95% CI: 0.6-0.9; P = 0.02) and OS (HR = 0.7; 95% CI: 0.6-1.0; P = 0.05). Expression of MMP-9 by lymphocytes correlated significantly with the degree of peritumoural inflammation (P = 0.02) but not with RFS (HR = 0.9; 95% CI: 0.7-1.1; P = 0.2) or OS (HR = 0.8; 95% CI: 0.7-1.0; P = 0.07). Conclusion: TIMP-1 in cancer cells is associated with poor prognosis independent of its function as inhibitor of MMP-9. MMP-9 and TIMP-1 are important mediators of the host-cancer cell interaction in the tumour microenvironment with significant influence on the histopathology and on prognosis of CRC.

KW - Adult

KW - Aged

KW - Colorectal Neoplasms

KW - Disease-Free Survival

KW - Female

KW - Humans

KW - Immunohistochemistry

KW - Male

KW - Matrix Metalloproteinase 9

KW - Microscopy, Electron

KW - Middle Aged

KW - Neoplasm Metastasis

KW - Neoplasm Proteins

KW - Prognosis

KW - Stromal Cells

KW - Tissue Inhibitor of Metalloproteinase-1

KW - Tumor Cells, Cultured

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DO - 10.1016/j.ejca.2010.07.046

M3 - Journal article

C2 - 20801641

SN - 0959-8049

VL - 46

SP - 3233

EP - 3242

JO - European journal of cancer (Oxford, England : 1990)

JF - European journal of cancer (Oxford, England : 1990)

IS - 18

ER -