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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

in vivo

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.
  • interferon-ß (IFN-ß)
  • 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.

in vitro

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?

  • Past 50 years
  • Wild, solitary, mole rat
  • Long life span (>20 yrs)
  • 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:

1. VEGF

2. p53

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

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