Stephen Paget “seed-soil”
- 1994: 76 articles
- 2004: 331 (3 folds/1decade)
- 2010: 4861 (15 folds/ half decade)
- ‘Ping-pong’ experiments (IP Witz Cancer Res, 1989)
- BALB/c 3T3 in vitro- in vivo injection (ping)
- Recultured from in vivo tumor (pong)
- In vivo passage cells was considerably augmented as compared to that of in vitro maintained clonal ancestors.
- In vivo “TME induces of pro-tumor effect.”
- Class II cancer gene (R. Sager PNAS, 1997)
- Many of class II genes are regulated by TME.
- Shifting focus from DNA to RNA
Non-tumor cells in TME are different from those in normal ME.
- Structural and functional alteration in TME
- Paracrine signal from tumor cell or normal cell
- Promalignant factors in TME
- Hypoxia (necrosis) in TME
- Low glucose concentration in TME
- Normalization of abnormal non-tumor constituents may reduce the malignancy phenotype?
- Tumor reversion is, indeed, possible?
- Not sufficiently cured by tumor cell eradication alone?
- Is there a hierarchy of interaction?