In a study of plasma and tissue platelet derived growth factor (PDGF) concentration in patients with breast cancer, elevated levels of plasma PDGF were found in a significant proportion, 11/37 (30%), of patients. Sixteen patients (43%) had tumors which expressed PDGF-AA and 6 patients had tumors which in addition expressed the BB isoform of PDGF. All patients with elevated plasma levels of platelet derived growth factor had tumors which expressed the growth factor on immunohistochemical staining of tumor cells. Furthermore there was a significant correlation between plasma levels of platelet derived growth factor and the intensity of tissue staining. Patients with stage four breast cancer with tumors which were positive for platelet derived growth factor had a significantly lower response rate to chemotherapy as well as significantly shorter duration of survival. In addition, patients with stage four breast cancer who had elevated plasma PDGF levels had a significantly shorter survival. These results indicate that elevated plasma levels of platelet derived growth factor in patients with breast cancer are derived from the tumor cells and suggest that platelet derived growth factor may play a significant role in control tumor cell growth.

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Nine patients with prolonged (> 2 years) chronic phase chronic myeloid leukaemia (CML) were investigated for the presence of T-cell involvement in the leukemic clone. Pure populations of peripheral blood T-cell populations were obtained by culturing separated mononuclear cells in the presence of pokeweed mitogen and IL2, until cultures showed > 99% pure T-cells. Purified T-cells and bone marrow and peripheral blood hematopoietic precursors were analysed for the presence of bcr-abl mRNA transcripts following RNA extraction and message amplification using polymerase chain reaction. In none of the 9 patients was bcr-abl mRNA found in T-lymphocytes while in all cases such transcripts were found in bone marrow and peripheral blood hematopoietic cells. Failure to detect T-cell involvement in patients with prolonged chronic phase CML using techniques designed to enhance even low level involvement of these cell populations supports the view that acquisition of the Ph chromosome abnormality does not occur in the totipotent stem cells but in more committed precursor cell/s with multilineage capacity but which only rarely retain the capacity for T-cell differentiation.

The influence of extracellular matrix components and of extracellular matrix structure on in vitro cell growth was investigated in the UWOV2 (Pf), protein-free cell culture model. This cell line constitutively produces an ordered extracellular matrix in the absence of any exogenous protein or growth factor. Extracellular matrix from UWOV2 (Pf) cells was found to contain both transforming growth factor beta (TGF beta) and platelet-derived growth factor (PDGF), which were shown to have an autostimulatory role for UWOV2 (Pf) cell growth. Matrix structure was shown to be important for allowing expression of the functional activity of these two growth factors. In addition, a nonuniform distribution of PDGF, embedded within the matrix structure, was demonstrated by immunoelectronmicroscopy. Apart from these two well-defined growth factors, additional but as yet unidentified growth stimulatory factor(s) were extractable from UWOV2 (Pf) extracellular matrix. These investigations indicate the potential role of extracellular matrix both as a mechanism for concentrating as well as modulating the function of cellular growth factors.