Sex influences on tumor innervation

Area of Science:

• Oncology
• Neuroscience
• Immunology

Background:

• Peripheral solid tumors, including oral cancers and melanoma, are infiltrated by nerves.
• The role of sex in tumor innervation and its impact on the tumor-brain circuit is not well understood.

Purpose of the Study:

• To investigate the influence of sex on tumor innervation in oral cancers and melanoma.
• To assess the impact of sex on the tumor-brain neural circuit and associated behavioral changes.
• To evaluate the effects of standard cancer therapy on tumor innervation, metastasis, and the tumor-brain circuit.

Main Methods:

• Utilized syngeneic cell lines in mice to model oral cancer and melanoma.
• Quantified tumor growth, innervation density, and metastasis.
• Assessed behavioral changes and neural activation in the central nervous system (CNS) projection areas.
• Administered cisplatin and radiation therapy to evaluate treatment effects.

Main Results:

• Tumors grew slower and were more innervated in females compared to males.
• Treatment with cisplatin and radiation increased tumor innervation, particularly in females, and led to increased lung metastasis in treated females.
• While the tumor-brain circuit itself did not differ by sex, peripheral malignancies activated neurons and glia in CNS projection areas, an effect attenuated by treatment, correlating with improved behavior.

Conclusions:

• Sex significantly influences peripheral tumor innervation and the activation of CNS projection areas via the tumor-brain circuit.
• Standard cancer therapies can modulate tumor innervation and neural activation, leading to improved behavior.
• Targeting the tumor-brain circuit may offer novel therapeutic strategies for cancer patients.