Oral Presentation 14th International Biennial Conference on Metastasis Research 2012

Disseminated cancer cells from non-metastatic patients display tumorigenic potential in immunodeficient mice (#30)

Melanie Werner-Klein 1 , Steffi Treitschke 2 , Christian Werno 2 , Christoph Klein 2 3 , Lahiri Kanth Nanduri 3 , Sebastian Scheitler 3 , Petra Rummele 4 , Hans-Stefan Hofmann 5 , Christian Hafner 6 , Claus Lattrich 7 , Brigitte Rack 8
  1. Institute for Immunology, University of Regensburg, Regensburg, Germany
  2. ITEM Regensburg/Project Group: Personalized Tumor Therapy, Fraunhofer Regensburg, Regensburg, Germany
  3. Chair of Experimental Medicine, University of Regensburg, Regensburg, Germany
  4. Institute for Pathology, University of Regensburg, Regensburg, Germany
  5. Clinic for Thoracic Surgery, University of Regensburg, Regensburg, Germany
  6. Clinic for Dermatology, University of Regensburg, Regensburg, Germany
  7. Clinic for Gyneology, University of Regensburg, Regensburg, Germany
  8. Clinic for Gyneology, LMU Munich, Munich, Germany
In patients without metastatic disease, disseminated cancer cells (DCC) belong to the rarest cells in the human body and are found in about 20-50% of M0 stage patients at frequencies of 1-2 cells per million bone marrow cells (BM). Despite their rareness, their detection in BM or lymph nodes (LN) has been shown to be a strong predictor of outcome, which suggests that DCC comprise metastases founder cells. However, it has not been possible to generate xenograft tumors from DCC and consequently their relevance has been repeatedly questioned. Here we show that DCC can form tumors in NodScidIL2Rg-/- (NSG) mice and therefore provide direct evidence for their metastasiogenic potential. The DCC were isolated from diagnostic BM-aspirates or LN-samples of melanoma or Non-Small-Cell-Lung-Cancer (NSCLC) patients. Xenograft-tumors could be established when cells were transplanted either directly, even at low cell numbers (<10 cells), or after short in vitro culture and serially transplanted. To date, 6 out of 9 melanoma LN-samples and 4 out of 11 NSCLC-samples from BM or LN have formed tumors. Molecular genomic comparisons between ex vivo isolated DCC and xenografts are currently underway and will be presented. DCC expansion may pave the way for molecular and functional studies, which will eventually enable improved systemic therapies at the dark stage of minimal residual cancer to prevent lethal metastasis.