| Publication number |
CLPUB00019 |
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| Authors |
Flick J.T., Waldron J.A., Vesole D.H., Jagganath S., Hoover R.G., Yeh Y.C., Epstein J., Hsu S.M., Barlogie B. |
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| Title |
Transforming growth factor-alpha (TGFalpha) is prominently expressed by the malignant plasma cells of multiple myeloma (MM). |
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| Citation |
Blood 82 Suppl. 1:259a-259a(1993) |
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| Abstract |
TGFalpha is a highly conserved, potent cellular transforming/mitotic
peptide, generally thought to act in an autocrine/paracrine fashion via
the EGF receptor (EGFr). TGFalpha is thought to play a major role in a
variety of malignant neoplasms. We have shown that freshly harvested
malignant plasma cells of 26/30 MM patients produce the TGFalpha protein.
Benign plasma cells were consitently TGFalpha negative. We confirmed that
TGFalpha production occurs at the mRNA level in 5/9 MM malignant plasma
cell lines, using a PCR method. We were able to induce TGFalpha mRNA in
all 9 MM cell lines after induction with TPA, an agent known to induce
TGFalpha in a variety of other cell types. Having established that
TGFalpha is produced by malignant plasma cells, we then focused on
determining the role of TGFalpha in the pathogenesis of MM. We observed
that the malignant plasma cells were consistently EGFr negative. Recent
studies have shown that differentiated cells such as eosinophils, neurons,
macrophages and fibroblasts can produce TGFalpha, suggesting that TGFalpha
may have actions other than a direct EGFr-mediated transforming/mitotic
process. Since TGFalpha did not appear to act on the malignant plasma
cells via the EGFr, we considered the possibility that the TGFalpha might
act indirectly invivo on other nearby cells, such as stromal cells or
myeloma progenitor cells. Analysis of stromal cultures harvested from the
bone marrow of 12 MM patients revealed that TGFalpha can induce the
stromal cells to produce increased amounts of IL6, a cytokine known to be
important in the growth and maintenance of MM (P<.05). The prominent
TGFalpha production by malignant plasma cells may thus stimulate stromal
cells, which in turn produce IL6 to cause proliferation/maturation of
myeloma precursor cells. We believe that TGFalpha (and IL6) are part of a
group of several growth factors/cytokines that interact to maintain the
malignant plasma cells of MM.
|
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| Cell lines |
CVCL_W396; ARH-DR CVCL_W397; SMITH CVCL_W398; TRAMA |
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