Hormones on Human Colon Cancer Cells Characterization of Functional Receptors for Gastrointestinal

نویسندگان

  • H. Frucht
  • A. F. Gazdar
  • J-A. Park
  • H. Oie
  • R. T. Jensen
چکیده

Studies demonstrate that some colon cancers possess receptors for various gastrointestinal hormones or neurotransmitters, the occupation of which can affect growth. These results are limited because frequently only a small number of tumors are studied, only 1 or 2 receptors are sought, and the effect on cell function is not investigated. In the present study, 10 recently characterized human colon cancer cell lines were studied to determine whether they possess receptors for any of 12 different gastrointestinal hormones or neurotransmitters and to determine whether these receptors mediate changes in cellular function. Each of the cell lines exhibited receptors for at least one radioligand. Receptors for vasoactive intestinal peptide (VIP) and muscarinic cholinergic agents occurred on 60%, bombesin and gastrin on 30%, /9-adrenergic agents and gastrin-releasing peptide (GRP) on 20%, and somatostatin, opiates, neuromedin B, and substance P on 10%. Analysis of |3H|./V-niethylscopolamine binding revealed a A,,of 0.2 n\i for A'-methylscopolamine with a binding capacity of 2500 sites/cell. With the agonist carbamylcholine, the receptor exhibited 2 classes of binding sites: one of high affinity (A(l 55 MM)representing 75% of the binding sites and one of low affinity (A"d 0.3 mM) representing 25% of the binding sites. Analysis of '"I-fTyr4] bombesin binding revealed a receptor of high affinity (A,, 2.1 /AI) with a binding capacity of 3300 sites/cell. Inhibition of binding by agonists revealed relative potencies of l2SI-[Tyr'|bombesin > GRP » neuromedin B, and two recently described antagonists were similar in potency to GRP. Analysis of '"I-VIP binding revealed a receptor having 2 classes of binding sites: one of high affinity (A',i3.6 n\i) and one of low affinity (A., 1.7 UM) which represented the majority of the 5.5 x 10'' binding sites/cell. The relative potencies of agonists were VIP > helodermin > peptide histidine methionine > secretin. Evaluation of biological activity mediated by the muscarinic cholinergic and bombesin receptors revealed an increase of intracellular calcium and of inositol triphosphate by specific receptor agonists. The presence or absence of receptors detected by binding correlated closely with the ability of selective receptor agonists to alter cell function. These results demonstrate the presence of several different receptors for gastrointestinal hormones or neurotransmitters, some described for the first time, on human colon cancer cell lines, including bombesin-related peptides, VIP, somatostatin, substance P, ßadrenergic agents, calcitonin gene-related peptide, gastrin, muscarinic cholinergic agents, and opiates. These receptors are functional because occupation by selective agonists altered intracellular mediators. These results suggest that it will be important to extend these studies to evaluate growth effects.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Characterization of functional receptors for gastrointestinal hormones on human colon cancer cells.

Studies demonstrate that some colon cancers possess receptors for various gastrointestinal hormones or neurotransmitters, the occupation of which can affect growth. These results are limited because frequently only a small number of tumors are studied, only 1 or 2 receptors are sought, and the effect on cell function is not investigated. In the present study, 10 recently characterized human col...

متن کامل

Vanadium Complexes with Maltol and Deferiprone Ligands: Synthesis, Characterization and In vitro Antiproliferative Activity toward Different Cancer Cells

In a systematic effort to identify a potent antiproliferative agent, four complexes of vanadium containing maltol and deferiprone ligands were synthesized and evaluated for their cytotoxic activity against five human and animal cancer cell lines, including human breast cancer cells (MCF-7), human cervix epithelial carcinoma (HeLa), human colon cancer cell line (HT-29), human leukemia cell line ...

متن کامل

The Serotonin 5-HT2A Receptor Antagonist Ritanserin Induces Apoptosis in Human Colorectal Cancer and Acts in Synergy with Curcumin

Curcumin exhibits both cancer- preventive activity and growth inhibitory effects on several neoplastic cells including human colon cancer. Serotonin and its receptors have also been implicated in tumor development. This study investigated the effect of ritanserin, a selective serotonin 5HT2A receptor antagonist, alone and in combination with curcumin on colorectal cancer cell lines. Result...

متن کامل

Preclinical study of a new 177Lu-labeled somatostatin receptor antagonist in HT-29 human colorectal cancer cells

Objective(s): Somatostatin receptor-positive neuroendocrine tumors have been targeted using various peptide analogs radiolabeled with therapeutic radionuclides for years. The better biomedical properties of radioantagonists as higher tumor uptake make these radioligands more attractive than agonists for somatostatin receptor-targeted radionuclide therapy. In this study...

متن کامل

The effect of gold nanoparticles on dose enhancement factor of human intestinal colon cancer HT-29 cells

Introduction: Radiation therapy is an important procedure for treatment of more than half of tumors. One way to increase the efficiency of radiation therapy is application of radiosensitizer at the site of tumor. gold nanoparticles (GNPs) have several characteristics that make them attractive for using with radiation therapy including small size (1–100 nm), biocompatibility, pr...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2006