Characterization of centriole duplication in human epidermis, Bowen's disease, and squamous cell carcinoma

Abstract

Background: Centrosomes contain two centrioles: a pre-existing mature centriole and a newly formed immature centriole. Each centriole is duplicated once within a cell cycle, which is crucial for proper centrosome duplication and cell division.

Objective: To describe the centrosome duplication cycle in human epidermis, Bowen's disease (BD), and squamous cell carcinoma (SCC).

Methods: Immunofluorescent staining of centriolar proteins and Ki-67 was used to evaluate cell cycles and the number of centrioles. Centrobin and Outer dense fiber of sperm tails 2 (ODF2) were used as markers for immature and mature centrioles, respectively.

Results: Normal human primary epidermal keratinocytes in a monolayered culture have one centrobin⁺ centriole (CTRB¹⁺ cells) supposed in G0/G1 phases or have two centrobin⁺ centrioles (CTRB²⁺ cells) supposed in S-G2 phase. In a three-dimensional culture and in vivo human epidermis, the majority of suprabasal cells were CTRB²⁺ cells, in spite of their non-proliferative Ki-67^- nature. The tumor mass of BD and SCC contained CTRB¹⁺ cells and Ki-67⁺ proliferating and Ki-67^- non-proliferative CTRB²⁺ cells. Clumping cells in BD had increased numbers of centrioles, with an approximate 1:1 to 2:1 ratio of centrobin⁺ to ODF2⁺ centrioles.

Conclusions: The cell cycle arrest of suprabasal cells is distinct from the G0 arrest of monolayered epithelial cells. Tumor mass of BD and SCC contained non-proliferative cells with the characteristics of the suprabasal cells of normal epidermis. A constant ratio of the number of centrobin⁺ to ODF2⁺ centrioles indicates that multiple centrioles were induced by cell division failure rather than centriole overduplication in clumping cells.

Keywords: Bowen's disease; Cell cycle; Centriole; Centrosome; Clumping cells.