Metastasis signatures: genes regulating tumor-microenvironment interactions predict metastatic behavior

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• The traditional multistep carcinogenesis model suggested metastasis arises from rare mutations in a small cell fraction.
• Emerging data challenge this, indicating metastasis is linked to widespread genetic events in the primary tumor mass.

Purpose of the Study:

• To review current understanding of gene expression in primary tumors and metastasis.
• To explore how primary tumor and microenvironment gene expression influence metastasis.
• To propose how this knowledge can aid in secondary cancer prevention.

Main Methods:

• Analysis of differential gene expression between primary tumors and metastases.
• Functional analysis of potential metastasis-associated genes in experimental metastasis models.

Main Results:

• Identification of numerous metastasis-associated gene expression events correlating with metastasis development.
• Recognition that metastasis-promoting genes include those from the tumor microenvironment and those involved in tumor-host interactions.

Conclusions:

• Metastasis is significantly influenced by gene expression patterns present in the majority of primary tumor cells and the surrounding microenvironment.
• Understanding these gene expression events offers potential for developing tools for secondary cancer prevention.