Immunolocalization of cell proliferation and tumor markers in the regenerating tail of the lizard Podarcis muralis likely involved in cell proliferation control.

Abstract

Purpose: The lizard blastema expresses typical genes present in cancer cells, and CD44 and S100A4 markers are known to be associated with metastasis, a process that is absent during tail regeneration in lizard.

Method: The present immunohistochemical study analyzes the distribution of hyaluronate, its main receptor CD44, and S100A4 (metastasin-1) in relation to proliferating cells in the early regenerating tail of the lizard Podarcis muralis.

Results: The regenerating blastema contains sparse proliferating cells immersed in a hyaluronate-rich extracellular matrix and these cells show a diffuse labeling for CD44 and S100A4. These proteins are more intensely localized in the apical regenerating (wound) epidermis and ependymal ampulla (regenerating spinal cord), two tissues essential for the stimulation of tail regeneration in lizards. Both markers generally show a cytoplasmic localization, but also a nuclear labeling is present in basal cells of the regenerating epidermis in the blastema, especially for S100A4. The latter protein is highly expressed in differentiating epidermis of regenerating scales, especially in the forming beta-layer.

Conclusions: The expression of these two marker oncoproteins, however, like others previously studied, is not associated with metastasis in the lizard blastema that instead develops into a new tail. The activation of cancer marker genes and proteins in the regenerating blastema does not determine degeneration into a tumor outgrowth. This process remains so far unexplained but is worth of a detailed molecular and cellular analysis aiming to find key processes on this physiological mechanism of tumor self-remission.