Nonhematopoietic tumor cells express functional GM-CSF receptors

Abstract

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates the colony growth of myeloid progenitors in semisolid media, and enhances the function of mature effector cells, including neutrophils, monocytes, and eosinophils. Small cell carcinoma lines (SCCL) have properties of amine precursor uptake and decarboxylation (APUD) cells and express high levels of the enzyme, L-aromatic amino acid decarboxylase. We looked for possible expression of GM-CSF receptors on nonhematopoietic cells and found specific high-affinity binding of human GM-CSF to SCCL and to the SV40-transformed African green monkey kidney cell line, COS. The small cell carcinoma lines responded to GM-CSF with enhanced proliferation, and both small cells and COS cells were found to express authentic 84,000 dalton GM-CSF receptor protein. These findings indicate that nonhematopoietic cells can bind and respond to GM-CSF, suggesting additional biological activities as well as the possibility of tumor responses when GM-CSF is used therapeutically in humans. Since preliminary clinical trials using CSFs as adjunctive treatment in patients with solid tumors are underway, it will be important to consider the possible responsiveness of nonhematopoietic tumor cells to CSFs.

Frequent expression of receptors for granulocyte‐macrophage colony‐stimulating factor on human nonhematopoietic tumor cell lines

“…This study revealed that 9 of 35 (26%) nonhematopoietic tumor cell lines expressed GM-CSF receptors. Although previous reports described that GM-CSF receptors were expressed on SCLC cells, but not on non-SCLC cells (Baldwin et al, 1989), we did not detect the significant binding of GM-CSF to SCLC cells which we tested. In contrast, GM-CSF receptors were expressed on 3 of 9 non-SCLC cells (Table 1).…”

“…Present results indicated that GM-CSF receptors are frequently expressed on non-SCLC cells rather than SCLC cells. The previous report described that only SCLC cells expressed GM-CSF receptors (Baldwin et al, 1989), and no report described the distribution of GM-CSF receptors on non-SCLC cells. The difference between previous reports and present one may be due to instability of cellular characteristics of lung cancer including surface receptor molecules.…”

“…Previous reports describing the growth promoting effects of GM-CSF on SCLC, breast cancer, co-lon cancer, and osteosarcoma cells suggested the existence of functional GM-CSF receptors on nonhematopoietic tumors (Dedhar et al, 1988;Baldwin et al, 1989;Berdel et al, 1989). However, only one report described the existence of the high affinity GM-CSF receptors on two SCLC cell lines whose growth were stimulated by GM-CSF (Baldwin et al, 1989). We also studied the biological effects of GM-CSF on nonhematopoietic tumor cell lines by ordinary colony formation assay in soft agar under various conditions.…”

“…It was first reported that GM-CSF inhibited the growth of SCLC cell lines with inducing myeloid differentiation (Ruff et al, 1986). However, the recent report described that GM-CSF stimulated the growth of SCLC cell lines, identifying the high affinity receptors with a n equilibrium dissociation constant (Kd) of approximately 20 pM on the SCLC cell lines (Baldwin et al, 1989). Subsequently, other reports showed that GM-CSF stimulated the growth of two osteosarcoma cell lines, a breast cancer cell line and two colon cancer cell lines, but the GM-CSF receptors on these tumor cells have not been characterized (Dedhar et al, 1988;Berdel et al, 1989).…”

In vivoactivation of JAK2/STAT‐3 pathway during angiogenesis induced by GM‐CSF

“…Several studies have suggested that GM-CSF responsiveness may not be limited to hematopoietic lineages (26)(27)(28)(29)(30)(31). Endothelial cells (EC) respond to GM-CSF (32,33) and express both GM-CSFR subunits (17,33).…”