The role of GM-CSF in lung cancer: a review of the literature

Abstract

The first hematopoietic growth factor, erythropoietin was discovered by Carnot and Deflandre in the early 1900’s when they showed that plasma from anemic animals would induce erythrocytosis in normal rabbits [l]. It was not until 60 years later that growth factors for myeloid and monocytic cells were described. The discovery of these hematopoietic growth factors was made possible by the development of semi-solid media to grow colonies of normal human bone marrow. Bradley and Metcalf [2] described methods for growing murine hematopoietic progenitor cells, and Robinson and Pike [3] refined these techniques and described methods for growing human progenitor cells in vitro. They subsequently showed that plasma from infected patients and supernatants from human cells infected with bacteria would increase the number of these bone marrow colonies and were thus termed colony stimulating factors or CSFs [4]. Much of the early work was conducted at the Walter and Eliza Hall Institute in Melbourne. Fig. 1 shows a photograph of some of the important scientists in the group at the time. The development of clinical application of the colony stimulating factors awaited the purification of the individual proteins, the cloning of their genes and the expression of these genes in bacterial and yeast cells to mass produce the factors [5,6]. At present, there are over 19 distinct factors which stimulate the growth of various cell lineages within the marrow. This paper will focus on studies of granulocyte macrophage colony stimulating factor (GM-CSF) in human lung cancer. Some studies evaluating other myeloid and monocyte growth factors such as granulocyte colony stimulating factor (GCSF), macrophage colony stimulating factor (M-CSF) and multi-CSF (IL-3) and some studies evaluating GM-CSF in other conditions will also be discussed briefly.