Two distinct expression patterns of urokinase, urokinase receptor and plasminogen activator inhibitor-1 in colon cancer liver metastases

Martin Illemann; Nigel Bird; Ali Majeed; Ole D Laerum; Leif R Lund; Keld Danø; Boye Schnack Nielsen

doi:10.1002/ijc.24166

Two distinct expression patterns of urokinase, urokinase receptor and plasminogen activator inhibitor-1 in colon cancer liver metastases

Martin Illemann, Nigel Bird, Ali Majeed, Ole D Laerum, Leif R Lund, Keld Danø, Boye Schnack Nielsen

Glycomics Program

68 Citations (Scopus)

Abstract

Metastatic growth and invasion by colon cancer cells in the liver requires the ability of the cancer cells to interact with the new tissue environment. Plasmin(ogen) is activated on cell surfaces by urokinase-type PA (uPA), and is regulated by uPAR and plasminogen activator inhibitor-1 (PAI-1). To compare the expression patterns of uPA, uPAR and PAI-1 in colon cancer with that in their liver metastases, we analysed matched samples from 14 patients. In all 14 primary colon cancers, we found upregulation of uPAR, uPA mRNA and PAI-1 in primarily stromal cells at the invasive front. In 5 of the 14 liver metastases, we found intense expression of uPAR, uPA-mRNA and PAI-1 in primarily stromal cells at the metastases periphery, and in an expression pattern similar to that found in the primary tumours. In the remaining 9 liver metastases, uPAR and uPA-mRNA were only seen associated with the presence of necrosis within the liver metastases. In addition, PAI-1-immunoreactivity was in all liver metastases seen in hepatocytes at the metastases periphery. Interestingly, the former 5 liver metastases positive for uPAR, uPA mRNA and PAI-1 at the metastasis periphery all had a predominantly desmoplastic reaction, whereas 8 of the remaining 9 showed direct contact between the cancer cells and the liver parenchyma. We conclude that there are 2 distinct patterns of expression of uPAR, uPA and PAI-1 in colon cancer liver metastases and that these correlate closely with 2 morphological growth patterns. These findings may have implication for the treatment of patients with metastatic disease.

Original language	English
Journal	International Journal of Cancer
Volume	124
Issue number	8
Pages (from-to)	1860-1870
Number of pages	11
ISSN	0020-7136
DOIs	https://doi.org/10.1002/ijc.24166
Publication status	Published - 2009

Keywords

Adenocarcinoma
Colonic Neoplasms
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Hepatocytes
Humans
Liver Neoplasms
Microscopy, Confocal
Microscopy, Fluorescence
Models, Biological
Neoplasm Invasiveness
Neoplasm Metastasis
Plasminogen Activator Inhibitor 1
Receptors, Urokinase Plasminogen Activator
Urokinase-Type Plasminogen Activator

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/ijc.24166

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@article{3f8e437059a811df928f000ea68e967b,

title = "Two distinct expression patterns of urokinase, urokinase receptor and plasminogen activator inhibitor-1 in colon cancer liver metastases",

abstract = "Metastatic growth and invasion by colon cancer cells in the liver requires the ability of the cancer cells to interact with the new tissue environment. Plasmin(ogen) is activated on cell surfaces by urokinase-type PA (uPA), and is regulated by uPAR and plasminogen activator inhibitor-1 (PAI-1). To compare the expression patterns of uPA, uPAR and PAI-1 in colon cancer with that in their liver metastases, we analysed matched samples from 14 patients. In all 14 primary colon cancers, we found upregulation of uPAR, uPA mRNA and PAI-1 in primarily stromal cells at the invasive front. In 5 of the 14 liver metastases, we found intense expression of uPAR, uPA-mRNA and PAI-1 in primarily stromal cells at the metastases periphery, and in an expression pattern similar to that found in the primary tumours. In the remaining 9 liver metastases, uPAR and uPA-mRNA were only seen associated with the presence of necrosis within the liver metastases. In addition, PAI-1-immunoreactivity was in all liver metastases seen in hepatocytes at the metastases periphery. Interestingly, the former 5 liver metastases positive for uPAR, uPA mRNA and PAI-1 at the metastasis periphery all had a predominantly desmoplastic reaction, whereas 8 of the remaining 9 showed direct contact between the cancer cells and the liver parenchyma. We conclude that there are 2 distinct patterns of expression of uPAR, uPA and PAI-1 in colon cancer liver metastases and that these correlate closely with 2 morphological growth patterns. These findings may have implication for the treatment of patients with metastatic disease.",

keywords = "Adenocarcinoma, Colonic Neoplasms, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Hepatocytes, Humans, Liver Neoplasms, Microscopy, Confocal, Microscopy, Fluorescence, Models, Biological, Neoplasm Invasiveness, Neoplasm Metastasis, Plasminogen Activator Inhibitor 1, Receptors, Urokinase Plasminogen Activator, Urokinase-Type Plasminogen Activator",

author = "Martin Illemann and Nigel Bird and Ali Majeed and Laerum, {Ole D} and Lund, {Leif R} and Keld Dan{\o} and Nielsen, {Boye Schnack}",

year = "2009",

doi = "10.1002/ijc.24166",

language = "English",

volume = "124",

pages = "1860--1870",

journal = "Radiation Oncology Investigations",

issn = "0020-7136",

publisher = "JohnWiley & Sons, Inc.",

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TY - JOUR

T1 - Two distinct expression patterns of urokinase, urokinase receptor and plasminogen activator inhibitor-1 in colon cancer liver metastases

AU - Illemann, Martin

AU - Bird, Nigel

AU - Majeed, Ali

AU - Laerum, Ole D

AU - Lund, Leif R

AU - Danø, Keld

AU - Nielsen, Boye Schnack

PY - 2009

Y1 - 2009

N2 - Metastatic growth and invasion by colon cancer cells in the liver requires the ability of the cancer cells to interact with the new tissue environment. Plasmin(ogen) is activated on cell surfaces by urokinase-type PA (uPA), and is regulated by uPAR and plasminogen activator inhibitor-1 (PAI-1). To compare the expression patterns of uPA, uPAR and PAI-1 in colon cancer with that in their liver metastases, we analysed matched samples from 14 patients. In all 14 primary colon cancers, we found upregulation of uPAR, uPA mRNA and PAI-1 in primarily stromal cells at the invasive front. In 5 of the 14 liver metastases, we found intense expression of uPAR, uPA-mRNA and PAI-1 in primarily stromal cells at the metastases periphery, and in an expression pattern similar to that found in the primary tumours. In the remaining 9 liver metastases, uPAR and uPA-mRNA were only seen associated with the presence of necrosis within the liver metastases. In addition, PAI-1-immunoreactivity was in all liver metastases seen in hepatocytes at the metastases periphery. Interestingly, the former 5 liver metastases positive for uPAR, uPA mRNA and PAI-1 at the metastasis periphery all had a predominantly desmoplastic reaction, whereas 8 of the remaining 9 showed direct contact between the cancer cells and the liver parenchyma. We conclude that there are 2 distinct patterns of expression of uPAR, uPA and PAI-1 in colon cancer liver metastases and that these correlate closely with 2 morphological growth patterns. These findings may have implication for the treatment of patients with metastatic disease.

AB - Metastatic growth and invasion by colon cancer cells in the liver requires the ability of the cancer cells to interact with the new tissue environment. Plasmin(ogen) is activated on cell surfaces by urokinase-type PA (uPA), and is regulated by uPAR and plasminogen activator inhibitor-1 (PAI-1). To compare the expression patterns of uPA, uPAR and PAI-1 in colon cancer with that in their liver metastases, we analysed matched samples from 14 patients. In all 14 primary colon cancers, we found upregulation of uPAR, uPA mRNA and PAI-1 in primarily stromal cells at the invasive front. In 5 of the 14 liver metastases, we found intense expression of uPAR, uPA-mRNA and PAI-1 in primarily stromal cells at the metastases periphery, and in an expression pattern similar to that found in the primary tumours. In the remaining 9 liver metastases, uPAR and uPA-mRNA were only seen associated with the presence of necrosis within the liver metastases. In addition, PAI-1-immunoreactivity was in all liver metastases seen in hepatocytes at the metastases periphery. Interestingly, the former 5 liver metastases positive for uPAR, uPA mRNA and PAI-1 at the metastasis periphery all had a predominantly desmoplastic reaction, whereas 8 of the remaining 9 showed direct contact between the cancer cells and the liver parenchyma. We conclude that there are 2 distinct patterns of expression of uPAR, uPA and PAI-1 in colon cancer liver metastases and that these correlate closely with 2 morphological growth patterns. These findings may have implication for the treatment of patients with metastatic disease.

KW - Adenocarcinoma

KW - Colonic Neoplasms

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Neoplastic

KW - Hepatocytes

KW - Humans

KW - Liver Neoplasms

KW - Microscopy, Confocal

KW - Microscopy, Fluorescence

KW - Models, Biological

KW - Neoplasm Invasiveness

KW - Neoplasm Metastasis

KW - Plasminogen Activator Inhibitor 1

KW - Receptors, Urokinase Plasminogen Activator

KW - Urokinase-Type Plasminogen Activator

U2 - 10.1002/ijc.24166

DO - 10.1002/ijc.24166

M3 - Journal article

C2 - 19123477

SN - 0020-7136

VL - 124

SP - 1860

EP - 1870

JO - Radiation Oncology Investigations

JF - Radiation Oncology Investigations

IS - 8

ER -

Two distinct expression patterns of urokinase, urokinase receptor and plasminogen activator inhibitor-1 in colon cancer liver metastases

Abstract

Keywords

UN SDGs

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