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Insulin‐like growth factor (IGF)–binding protein‐3 (IGFBP‐3) proteolysis in patients with colorectal cancer: possible association with the metastatic potential of the tumor
Author(s) -
Baciuchka Marjorie,
RemacleBonnet Maryse,
Garrouste Françoise,
Favre Roger,
Sastre Bernard,
Pommier Gilbert
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19981023)79:5<460::aid-ijc3>3.0.co;2-z
Subject(s) - proteolysis , in vivo , insulin like growth factor binding protein , endocrinology , medicine , protease , insulin like growth factor , growth factor , cancer , in vitro , insulin like growth factor 2 , biology , receptor , enzyme , biochemistry , microbiology and biotechnology
The limited proteolysis of insulin‐like growth factor (IGF)–binding protein (IGFBP)‐3 is a key event in the regulation of endocrine bioavailability of IGFs. Here, we investigated IGFBP‐3 and IGFBP‐3 proteolysis in serum from patients with colorectal cancer both before and at different times following surgery. In vivo IGFBP‐3 proteolysis, estimated by immunoblot analysis of IGFBP‐3 fragments in serum, and in vitro IGFBP‐3 protease activity of serum, estimated by a 125 I‐IGFBP‐3 degradation assay, allowed us to identify 2 groups of patients (IGF‐M vs. IGF‐NM) with respect to their status for mobilizing the IGF system. In IGF‐M patients , in vivo and in vitro IGFBP‐3 proteolysis were significantly elevated (156% and 181% of the age‐matched control pool, respectively) and accompanied by a decrease in intact IGFBP‐3 (38% of the control pool). The IGFBP‐3 proteolytic processing was further increased in response to surgical ablation of the tumor (mean increase 45–55%), then gradually returned to levels comparable with controls. In contrast, IGF‐NM patients exhibited a minimal alteration of in vitro IGFBP‐3 protease activity and even an inhibition of in vivo IGFBP‐3 proteolysis, whereas intact IGFBP‐3 was unaltered when compared with controls. Moreover, this pattern was not further significantly altered in response to the surgical stress. None (0/6) of the IGF‐M patients vs. 70% (5/7) of the IGF‐NM patients developed a metastatic disease (median duration of follow‐up 26 months). Neither elevated amounts of pro‐IGF‐II nor presence of detectable IGFBP‐3 protease inhibitors in the circulation could explain the observed suppression of IGFBP‐3 proteolytic processing in IGF‐NM patients. These results indicate that inhibition of IGFBP‐3 proteolysis and invasive properties of cancer cells are related in colorectal cancer patients. Int. J. Cancer (Pred. Oncol.) 79:460–467, 1998.© 1998 Wiley‐Liss, Inc.