Factor’s yin-yang tumor effectsJun. 10, 2013, 8:00 AM
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.