The challenge of tumor heterogeneity--different phenotypes of cancer stem cells in a head and neck squamous cell carcinoma xenograft mouse model.

BACKGROUND/AIM: Besides late diagnosis, tumor metastasis and cancer relapse are the main reasons for the poor prognosis of patients with head and neck cancer. Several investigations have shown that tumor is of heterogeneous molecularity consisting of several subpopulations, with a broad range of biological behaviors. The ability and potential of tumor to infiltrate into vessels and into neighbouring organs, as well as the resistance to chemotherapeutical cancer therapy may be caused by cancer stem cells (CSCs). The aim of the present study was to illuminate the role and behaviour of (CD44) and (ALDH1A1) as tumor stem cell markers in a xenograft mouse model of squamous cell carcinoma.

MATERIALS AND METHODS

Five female NMRI-Foxn1nu mice were injected with five million Detroit 562 cells (100 μl). After sacrifice of the mice, tumors were excised. Then ALDH1A1, CD44, (EGFR), CD31 and Ki 67 were detected as molecular markers for tumor stem cells by immunohistopathology and immunofluorescence.

RESULTS

The amount of putative CSC marker proteins CD44 and ALDH1A1 vary. ALDH1A1high tumor cells express low levels of CD44 and EGFR. The CD44+high expressers also exhibit expression of high levels of the EGFR. CSCs must be sub-classified depending on their expression of marker proteins.

CONCLUSION

We assume that CSCs can also be sub-classified into migratory and stationary CSCs. ALDH1A1high/CD44low/EGFRlow tumor cells may be stationary and quiescent, whereas ALDH1A1-/CD44high/EGFRhigh expressers have a migratory, invasive nature. It is likely that a regulatory mechanism, as yet unknown, controls this conversion, from quiescent to active cancer stem cells.