Polypeptide growth factors, regulatory peptides, and a variety of pharmacological agents acting alone or synergistically induce mitogenesis in cultured fibroblasts. The early signals in the membrane, cytosol, and nucleus promoted by these extracellular factors, together with their mitogenic effectiveness, are integrated in a unified hypothesis for the regulation of fibroblast growth.

https://science.sciencemag.org/content/sci/234/4773/161.full.pdf

Early signals in the mitogenic response

The autocrine hypothesis proposes that a cell produces and secretes a hormone-like substance that can interact with specific membrane receptors on its surface to induce effects such as proliferation. Thus, a cancer cell could act to stimulate its own growth. Bombesin and bombesin-like peptides (BLPs) such as gastrin-releasing peptide (GRP) cause various physiological responses in mammals, including stimulation of proliferation of 3T3 mouse fibroblasts and normal human bronchial epithelial cells in vitro and induction of gastrin cell hyperplasia and increased pancreatic DNA content in vivo in rats. Human small-cell lung cancer (SCLC) cell lines produce and secrete BLPs and can express a single class of high-affinity receptors for BLPs. Exogenously added BLPs can also stimulate the clonal growth and DNA synthesis of SCLC in vitro. These findings suggest that BLPs function as autocrine growth factors for this tumour. One way to test this hypothesis is to interrupt the function of the endogenously produced BLPs. Here, we demonstrate that a monoclonal antibody to bombesin binds to the C-terminal region of BLPs, blocks the binding of the hormone to cellular receptors and inhibits the clonal growth of SCLC in vitro and the growth of SCLC xenografts in vivo. These results demonstrate that BLPs can function as autocrine growth factors for human SCLC.

Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer.

Dipeptidyl-peptidase IV/CD26 (DPP IV) is a cell-surface protease belonging to the prolyloligopeptidase family. It selectively removes the N-terminal dipeptide from peptides with proline or alanine in the second position. Apart from its catalytic activity, it interacts with several proteins, for instance, adenosine deaminase, the HIV gp120 protein, fibronectin, collagen, the chemokine receptor CXCR4, and the tyrosine phosphatase CD45. DPP IV is expressed on a specific set of T lymphocytes, where it is up-regulated after activation. It is also expressed in a variety of tissues, primarily on endothelial and epithelial cells. A soluble form is present in plasma and other body fluids. DPP IV has been proposed as a diagnostic or prognostic marker for various tumors, hematological malignancies, immunological, inflammatory, psychoneuroendocrine disorders, and viral infections. DPP IV truncates many bioactive peptides of medical importance. It plays a role in glucose homeostasis through proteolytic inactivation of...

Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV.

Characterization of a gastrin releasing peptide from porcine non-antral gastric tissue.

Digestive enzymes in fish larvae and juveniles—implications and applications to formulated diets

This paper presents evidence for the existence in extracts from porcine non-antral gastric tissue of a peptide capable of causing substantial rises of plasma immunoreactive gastrin levels in a dose dependent manner and of stimulation of gastric acid and pepsin secretion. Obtained data show that the peptide is basic and that its gastrin releasing properties are at least partially resistant to atropinisation and beta-receptor blockade. Antrectomy almost eliminates the rise in plasma IRGa when the peptide is administered. The possible relationship of this peptide to amphibian bombesin is discussed.

https://gut.bmj.com/content/gutjnl/19/9/767.full.pdf

G. Nilsson

Papers

Characterization of a gastrin releasing peptide from porcine non-antral gastric tissue.

A gastrin releasing peptide from the porcine nonantral gastric tissue.