BACKGROUND
Spalax ehrenbergi
PURPOSE
To Prove:
- Spalax is resistant to experimentally induced cancer
- Spalax's normal fibroblasts target tumor cells and restrict malignant behavior
- direct fibroblast-cancer cell interaction
- soluble factors produced by Spalax fibroblasts
- Spalax is resistant to two-stage DMBA/TPA, and 3-MCA carcinogen treatments.
DISCUSSION & CONCLUSION
FIGURE 2
FIGURE 1
Conclusion
In vivo studies of carcinogen-induced
tumor
Can there possibly be cure of cancer?
FIGURE 4 & 5
Research on Spalax can be a key for understanding the molecular nature of host resistance to cancer and identify new anti-cancer strategies for treating humans.
RESULTS
DMBA/TPA
- (A) Spalax had necrotic wounds, later healed with no signs of malignancy.
- (B) Mice however, developed benign papillomas later transformed to squamous cell carcinomas
In vitro studies of Spalax cancer resistance
- The research conducted demonstrated that Spalax fibroblasts or their CM target human cancer cells growth machinery, triggering programmed cancer cell death.
- Following co-culture with Spalax fibroblasts or their CM, cancer cells (Hep3B, HepG2 and MCF7) undergo morphological changes typical of apoptosis: swelling, rounding, detachment, shrinkage and floating.
Presesnted by: Brittney Ferguson, Rhontasha Gerrick, Farhana Chowdury
FIGURE 3
FIGURE 6
3-MCA
- Spalax had no pathological process.
- Mice and rats were effected and all of them developed tumors at the injection site in matter of few months.
Example
RESULTS
- The effect of Spalax CM on cancer cells is transient and reversible.
- Spalax fibroblasts presumably impair the aggressive behavior of tumor cells: the invasive phenotype of highly metastatic MDA-MB-231 breast carcinoma cells was markedly reduced.
Pronounced cancer resistance in a subterranean rodent, the blind mole-rat, Spalax: in vivo and in vitro evidence
Where was the study conducted?
- Institute of Evolution of Haifa University
How long has the study been in progress?
- No spontaneous tumors or phenotypic signs of aging
- Inhabits poorly ventilated, dark underground tunnels
- Enables adaptations for survival
- Ability to cope with extreme Hypoxia and Hypercapnia
More on information on Spalax:
- Have genes with hypoxia-related adaptations:
BY: Irena Manov, Mark Hirsh, Theodore C Iancu, Assaf Malik, Nick Sotnichenko, Mark Band, Aaron Avivi, and Imad Shams
3. Spalax heparanase splice variant
METHODS
- Spalax transcriptome assembly and expression suggests resistance to malignant transformation
Experiment 1
Experiment 2
Fibroblasts
Focus:
- Spalax is resistant to spontaneous cancer
- Assuming normal fibroblasts played a role
- Use 2 step DMBA/TPA skin carcinogenesis protocol and 3MCA protocol for local fibrosarcoma induction
- mice, rats and Spalax
- in vivo
- co-culture (in vitro)
- study interactions between normal primary fibroblasts with:
- human hepatocellular carcinoma cells (Hep3B and HepG2)
- breast cancer cells (MDA-MB-231 and MCF7)
- 3MCA-induced, Spalax-derived fibrosarcoma cells (SpFS2240)
- stromal cells interlinked with tumors via:
- regulation of growth factors and cytokines
- reassembling of extracellular matrix (ECM)
Activated -> Cancer - enhancing effects
Normal -> tumor suppressor function