Category: Research
Pathology in TME Issue
Matrix(stroma) is included in your study?
- Cell-cell interaction/cell-matrix interaction/integral TME
- 75% quantity
- Mechanical stiffness manisfested as desmoplasia vs. fibrosis vs. elastosis? Hypoxic survival-related changes?
- Edema or myxoid degeneration by activated MMP prior to neovascularization?
Peri/intratumoral inflammatory TME?
- chemo/cytokine by TAM ½
- Double-edged sword for tumor/friend or foe?
Invasion onset biomarker?
- For very early onset of microinvasion? lymphovascular invasion implicaiton?
Metastasis plasticity-differentiation? Molecular similarity?
- Lastency/dormancy? CTC? Colonization?
TME “seed-soil”&“Ping-pong”
Stephen Paget “seed-soil”
- 1994: 76 articles
- 2004: 331 (3 folds/1decade)
- 2010: 4861 (15 folds/ half decade)
Post-Paget era
- ‘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
Question?
- 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?
Tumor microenvironment - Double-edged sword
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
Extracellular Matrix (ECM)
- Compression buffer with structural frame
- Cell-cell interaction regulation
- Blackbox (footpath)
- One thing arises from all things, and all things arise from one thing (Aristotle)
- Tumor migration
- Stiffness and destruction
- No de novo synthesis
◊ Proteoglycan
√ Heparan sulfate
√ Chondroitin sulfate
√ Keratan sulfate
◊ Non-proteoglycan
√ Fiber
√ Fibronectin
√ Collagen-14 types
√ Elastin
√ Laminin
√ Hyaluronic acid
Soil researcher as in Scientific Botanist
Cancer Interface Microenvironment Laboratory 
