Contemporary issue

• Cellular/ soluble factors

– Balance score of pro-(MCP-1, IL-6, MMP) and anti-malignant (IP-10)   factors: 1.36~ 2.44 (Witz, IJCa 2003)

– No MECE

• P-P interaction
• Tumor heterogeneity vs. signal heterogeneity
• Cross-talk (agonistic vs. antagonistic)

– TNF family

Proinflammatory cytokine as promalignant effect (since R. Virchow, 1863)

– TGF-β

> Inhibit normal mammary epithelail cells

> Enhance tumor cell invasion/mets:
– loss of anti-proliferative role
– mutation in TGFBR
– inhibition of SMAD pathway
– suppressing anti-tumor immune response
– augmenting angiogenesis