Aberrant expression of gastrin-releasing peptide and its receptor by well-differentiated colon cancers in humans

被引:88
作者
Carroll, RE
Matkowskyj, KA
Chakrabarti, S
McDonald, TJ
Benya, RV
机构
[1] Univ Illinois, Dept Med, Chicago, IL 60612 USA
[2] Chicago Vet Affairs Med Ctr, W Side Div, Chicago, IL 60612 USA
[3] Univ Western Ontario, Dept Pathol, London, ON N6A 5A5, Canada
[4] Univ Western Ontario, Dept Med, London, ON N6A 5A5, Canada
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 1999年 / 276卷 / 03期
关键词
adenocarcinoma; bombesin; mitogen; morphogen;
D O I
10.1152/ajpgi.1999.276.3.G655
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Epithelial cells lining the adult human colon do not normally express gastrin-releasing peptide (GRP) or its receptor (GRPR). In contrast, approximately one-third of human colon cancers and cancer cell lines have been shown to express GRP-binding sites. Because GRPR activation causes the proliferation of many cancer cell lines, GRP has been presumed to act as a clinically significant growth factor. Yet GRP has not been shown to be expressed by colon cancers in humans nor has the effect of GRP and/or GRPR coexpression on tumor behavior been investigated. We therefore determined GRP and GRPR expression by immunohistochemistry in 50 randomly selected colon cancers resected between 1980 and 1997, all 37 associated lymph node and liver metastases, and 20 polyps. Tumor sections studied were those that contained the margin and adjacent nonmalignant epithelium. Overall, 84% of cancers aberrantly expressed GRP or GRPR, with 62% expressing both ligand and receptor, whereas expression was not observed in adjacent normal epithelium. Consistent with the previously established mitogenic capabilities of GRP, tissues coexpressing GRP and GRPR were more likely to express proliferating cell nuclear antigen than tissues not expressing both ligand and receptor. Yet GRP/GRPR coexpression was seen with equal frequency in stage A as in stage D cancers and was only detected in 1 in 37 metastases. Furthermore, Kaplan-Meier analysis did not reveal any difference in patient survival between those whose tumors did or did not express GRP/GRPR. In contrast, GRP/GRPR coexpression was found in all well-differentiated tumor regions, whereas poorly differentiated tissues never coexpressed GRP/GRPR. Overall, these data indicate that, although GRP is a mitogen, it is not a clinically significant growth factor in human colon cancers. Rather, the strong association of GRP/GRPR coexpression with tumor differentiation raises the possibility that these proteins primarily act in vivo as morphogens.
引用
收藏
页码:G655 / G665
页数:11
相关论文
共 48 条
  • [1] NEUROPEPTIDES IN NEUROLOGICAL TUMORS
    ALLEN, JM
    HOYLE, NR
    YEATS, JC
    GHATEI, MA
    THOMAS, DGT
    BLOOM, SR
    [J]. JOURNAL OF NEURO-ONCOLOGY, 1985, 3 (03) : 197 - 202
  • [2] Allen T.C., 1992, LAB METHODS HISTOTEC, P53
  • [3] BOMBESIN RECEPTOR GENE-EXPRESSION DURING MAMMALIAN DEVELOPMENT
    BATTEY, J
    WADA, E
    WRAY, S
    [J]. MODELS OF NEUROPEPTIDE ACTION, 1994, 739 : 244 - 252
  • [4] BHARGAVA M, 1992, CELL GROWTH DIFFER, V3, P11
  • [5] IDENTIFICATION OF THE HEPATOCYTE GROWTH-FACTOR RECEPTOR AS THE C-MET PROTOONCOGENE PRODUCT
    BOTTARO, DP
    RUBIN, JS
    FALETTO, DL
    CHAN, AML
    KMIECIK, TE
    VANDEWOUDE, GF
    AARONSON, SA
    [J]. SCIENCE, 1991, 251 (4995) : 802 - 804
  • [6] CORJAY MH, 1991, J BIOL CHEM, V266, P18771
  • [7] BOMBESIN-LIKE PEPTIDES CAN FUNCTION AS AUTOCRINE GROWTH-FACTORS IN HUMAN SMALL-CELL LUNG-CANCER
    CUTTITTA, F
    CARNEY, DN
    MULSHINE, J
    MOODY, TW
    FEDORKO, J
    FISCHLER, A
    MINNA, JD
    [J]. NATURE, 1985, 316 (6031) : 823 - 826
  • [8] OCCURRENCE OF BOMBESIN AND ALYTESIN IN EXTRACTS OF SKIN OF 3 EUROPEAN DISCOGLOSSID FROGS AND PHARMACOLOGICAL ACTIONS OF BOMBESIN ON EXTRAVASCULAR SMOOTH MUSCLE
    ERSPAMER, V
    FALCONIE.G
    NEGRI, L
    INSELVINI, M
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1972, 45 (02) : 333 - +
  • [9] Constitutive activation of the gastrin-releasing peptide receptor expressed by the nonmalignant human colon epithelial cell line NCM460
    Ferris, HA
    Carroll, RE
    Rasenick, MM
    Benya, RV
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (10) : 2530 - 2537
  • [10] Location and characterization of the human GRP receptor expressed by gastrointestinal epithelial cells
    Ferris, HA
    Carroll, RE
    Lorimer, DL
    Benya, RV
    [J]. PEPTIDES, 1997, 18 (05) : 663 - 672