Neurotensin (NT), a distal gut
peptide released by intraluminal
fats, is trophic for normal small bowel and colonic mucosa. In addition, NT stimulates growth of certain
colon cancers; the mechanism for this effect is not known. The purpose of this study was to determine whether human
colon cancers (HCC) (1) express the
mRNA for NT/
neuromedin N (N), (2) produce NT
peptide, and (3) express the
mRNA for a functional NT receptor (NTR).
RNA was extracted from four HCC cell lines in culture, nine HCC lines established in athymic nude mice, and from six HCC and adjacent normal mucosa from freshly resected operative specimens; the
RNA was analyzed for NT/N
mRNA by Northern hybridization with a
complementary DNA probe.
Neurotensin peptide content, NTR expression, and intracellular Ca++ ([Ca++]i) mobilization in response to NT were evaluated in three HCC cell lines (LoVo, HT29, HCT116).
Neurotensin/N
mRNA transcripts were identified in all four of the HCC cell lines and in one of nine HCC in nude mice.
Neurotensin expression was found in two of six freshly resected HCC and in none of the six corresponding samples of normal mucosa.
Neurotensin peptide was identified by RIA in LoVo, HT29, and HCT116. In addition, NTR
mRNA was found in HT29 and HCT116.
Neurotensin stimulated [Ca++]i mobilization in HCT116 (without serum) and in LoVo (with 0.25% serum). These findings demonstrate the presence of NT/N
mRNA and NT
peptide and the presence of a functional NTR in certain HCC.
Neurotensin, a potent trophic factor for normal gut mucosa, may function as an autocrine
growth factor in certain human
colon cancers.