Metastatic Brain Tumors

In the natural course of malignant tumors, brain metastasis occurs in about 20-40% of patients. Metastasis of tumor cells is one of the most important features of malignant tumors, and the intra- and intercellular molecular mechanisms involved in the metastatic process are very complex. Alfa Cytology focuses on tumor cells undergoing epithelial-mesenchymal transition, circulating tumor cells surviving in blood vessels, tumor cell dormancy, tumor cell heterogeneity, and its stemness during brain metastasis to help you study a series of events related to tumor microenvironments such as tumor cell-stromal cell interaction and tumor-associated blood vessel formation.

Figure 1. Steps in the development of brain metastases in an animal model. (Steeg, P. S., et al., 2011)

Cell biological properties

• Tumor cells metastasize directly to form distant metastases without alteration.
• Tumor cells metastasize to distant organs, partially adapt to the microenvironment, and then produce certain changes to better adapt.
• The tumor primarily contains multiple subclonal cells with random mutations (including mutations with metastatic properties) that metastasize directly to distant organs and form metastatic foci.
• In cases where metastasis has formed, some of the tumor cells in the primary lesion can develop certain changes and enter that metastasis.
• In the early stage of the carcinogenesis process, some of the quasi-normal cells can colonize distant organs and produce mutations, and then proliferate to form metastases.

Whether this process occurs in the early stage of tumorigenesis, in the primary site, in the metastatic site, or during metastasis, the aim is to better adapt to the microenvironment of the distant organ. This change can be expressed at the DNA level or the epigenetic level, thus influencing the phenotypic changes of the tumor cells. We can help you interpret the biology of brain metastatic tumor cells in terms of genetic alterations, post-translational modifications, and metabolic characteristics.

Genetic alterations

Genomic alterations such as single nucleotide variation (SNV), copy number variation (CNV), deletion, amplification, etc. have been demonstrated between the genome of metastatic brain lesions and the primary lesions, and these genomic alterations mainly involve the activation of multiple cell signaling pathways, apoptosis, and cell adhesion and other functions. We will help you find this genetic alteration and assist you to study this series of alteration patterns and their generation mechanisms to help explain the mechanism of tumor brain metastasis formation, and also provide promising therapeutic targets for brain metastasis foci treatment.

Epigenetic alterations

• Methylation. altered methylation levels of tumor cells in central nervous system (CNS) may contribute to the altered tumor phenotype, and we can perform a comparison of genome-wide methylation levels of tumor cells in multiple cell lines in nude mouse brain metastasis versus subcutaneous tumor models, allowing you to explore the causes in greater depth.
• miRNAs. miRNAs are small non-coding RNAs of approximately 19 bp-25 bp in length that bind to mRNAs and then degrade or repress the corresponding mRNAs, thereby affecting gene expression. We can screen down-regulated miRNAs such as miR-145, miR-214, miR-9, and miR-1471 by comparing miRNA levels in primary lesions and brain metastases of cancer patients to help you study the key miRNAs that affect the proliferation and invasive ability of tumor cells.

Alfa Cytology provides you with research support and more information on many of the above brain metastases, offering a series of solutions for targeted drug development, molecular mechanism research, and in vitro model building for brain metastases tumors. Please feel free to contact us to submit your requirements for earlier communication of project details.

Reference

1. Steeg, P. S., et al. (2011). "Brain metastases as preventive and therapeutic targets." Nat Rev Cancer;11(5):352-363.