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Lung-derived growth factor that stimulates the growth of lung-metastasizing tumor cells: identification as
1Department of Tumor Biology, University of Texas M.D. Anderson Hospital and Cancer Center, Houston 77030.
Abstract:
We have previously shown that culture medium conditioned by lung fragments contains mitogenic activity for lung-metastasizing tumor cells but not for their non-metastatic counterparts. The growth-promoting component from media conditioned by rat and porcine lungs has been purified and partially characterized as a Mr approximately 66,000 (unreduced) or Mr approximately 72,000 (reduced) glycoprotein [Cancer Res 49:3928, 1989; J Cell Biochem 43:127, 1990]. Here we report that this factor is the iron transport protein transferrin. Migration distances in sodium dodecyl sulfate and native gel polyacrylamide electrophoresis systems were similar, as were the specific activities and spectrum of mitogenic activities of the lung-derived growth factor and transferrin. Electrophoretically separated holo-rat transferrin and rat lung-derived growth factor displayed similar positive stains for iron. A polyclonal antibody generated against the lung-derived growth factor cross-reacted with human and rat transferrin in Western blots, and anti-human transferrin cross-reacted with rat lung-derived growth factor. All of the mitogenic activity contained in crude lung conditioned media could be removed by antibody-mediated transferrin depletion. The putative cell receptor molecular weights for the lung-derived growth factor and transferrin were similar as were the molecular weights of polypeptides produced by partial trypsin cleavage of the two. Finally, the amino acid sequence of certain regions of rat lung-derived growth factor demonstrated a high degree of homology to human transferrin. The physical and biochemical properties, antigenicity, and mitogenic activity of a previously unidentified lung-derived growth factor for lung-metastasizing tumor cells indicate that it is transferrin.
Insights
Researchers identified a lung-derived growth factor that promotes lung metastasis in tumor cells. This factor was found to be the iron transport protein, transferrin, based on its biochemical properties and mitogenic activity.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Lung-conditioned media contains a mitogenic factor for lung-metastasizing tumor cells.
- Previous work characterized this factor as a glycoprotein of approximately 66-72 kDa.
Purpose of the Study:
- To identify the specific molecular identity of the lung-derived growth factor.
- To confirm if the factor is transferrin and elucidate its role in tumor cell growth.
Main Methods:
- Comparative analysis of migration patterns in gel electrophoresis.
- Iron staining and antibody cross-reactivity assays.
- Amino acid sequencing and receptor binding studies.
Main Results:
- The lung-derived growth factor exhibited identical electrophoretic mobility, iron staining, and mitogenic activity spectrum to transferrin.
- Antibodies against the factor cross-reacted with transferrin, and vice versa.
- Amino acid sequencing revealed high homology between the factor and human transferrin.
Conclusions:
- The previously unidentified lung-derived growth factor is transferrin.
- Transferrin promotes the growth of lung-metastasizing tumor cells.