CXCL12γ induces human prostate and mammary gland development

Area of Science:

• Cell Biology
• Stem Cell Research
• Cancer Biology

Background:

• Epithelial stem cells (ESCs) maintain tissue homeostasis; dysregulated ESCs can drive cancer.
• Reprogramming normal epithelial cells into stem-like cells aids understanding of cancer and normal gland development.
• Previous work linked CXCL12γ to cancer stem cells; its role in normal epithelial cell fate was unknown.

Purpose of the Study:

• To investigate the functional role of CXCL12γ in regulating epithelial stem cells (ESCs).
• To elucidate CXCL12γ's function in normal prostate and mammary epithelial cell development.
• To understand how CXCL12γ influences normal gland development and tissue homeostasis.

Main Methods:

• Overexpressed CXCL12γ in prostate (PNT2) and mammary (MCF10A) epithelial cells.
• Utilized quantitative real-time PCR, Western blots, and immunofluorescence for marker analysis.
• Employed fluorescence-activated cell sorting and sphere formation assays for stem cell phenotype and function.
• Evaluated gland/acini formation in vivo using xenotransplantation animal models.

Main Results:

• CXCL12γ overexpression reprogrammed luminal epithelial cells to a nonluminal phenotype in both prostate and mammary cells.
• CXCL12γ-induced nonluminal cells exhibited an increased epithelial stem-like phenotype (EPCAM^Lo/CD49f^Hi/CD24^Lo/CD44^Hi).
• Overexpression of CXCL12γ promoted robust gland-like structure formation in vivo.

Conclusions:

• CXCL12γ drives the reprogramming of epithelial cells into nonluminal stem cells.
• This reprogramming process is crucial for facilitating gland development.
• CXCL12γ plays a key role in regulating epithelial stem cell fate and tissue development.