Tumor necrosis factor-alpha (TNF-alpha) is produced by most malignant cells, but its role in cancer progression – pro- or anti-tumor – is conflicting.
Pampee Young, M.D., Ph.D., and colleagues including Pierre Massion, M.D., explored whether the two different forms of TNF-alpha – membrane-bound (mTNF-alpha) and soluble (sTNF-alpha) – have distinct actions that contribute to the varying findings. Using mouse lung and melanoma tumor cell lines, they demonstrated that sTNF-alpha (the more studied form) promotes cancer growth and mTNF-alpha inhibits tumor growth by reducing the number of tumor-associated myeloid cells. They also found that human non-small cell lung cancer tissues have differing expression of membrane versus soluble TNF-alpha, and that patients whose tumors had gene “signatures” consistent with higher levels of mTNF-alpha had improved survival compared to tumors with more sTNF-alpha.
The findings, reported in the journal Cancer Research, suggest that the two forms of TNF-alpha have opposing effects on tumor progression – an insight that is critical for the effective use of TNFa inhibitors, which can block both forms.
This research was supported by grants from the National Institutes of Health (HL088424, RR024975, CA090949, HL069765) and by a Veterans Affairs Merit Award.
