Christer Ericsson Project
Circulating Tumor Cells, metastasis and "minimal residual disease"
Ideally cancer diagnosis should be based on the properties of those tumor cells that have reached the blood, the circulating tumor cells (CTC), and are in the process of spreading the cancer to form distant metastases. About 90% of deaths from cancer are associated with metastases, not the primary tumor. Metastases localize in a typical pattern for each form of cancer. We seek to understand the properties of circulating tumor cells that are relevant for the spread of cancer.
The circulating tumor cells are sub-clones of the primary tumor that, in contrast to normal mature epithelial cells, have acquired motile properties. Those properties allow them to dissociate from their normal fairly fixed place, move towards and invade the blood vessels. Once in the blood, the vast majority of the circulating tumor cells die from natural causes, but a few survive, and a fateful few of those also attach at distant organs where they may exit the circulation and lodge in a distant organ. To actually grow and divide requires that they also have acquired cancer stem cell properties. Furthermore, they need to receive a grow-and-divide queue from their environment. This may happen only years later.
It is believed that the invasive and cancer stem cell properties come about through inappropriate re-activation of a normal cellular program used in embryonic development, called epithelial-to-mesenchymal transition (EMT), and its reverse mesenchymal-to-epithelial transition (MET). Thus in order to rationally diagnose and treat metastatic cancer requires knowing the relevant regulatory and functional pathways of the circulating tumor cells, and then designing generic or targeted treatment modalities to the key driver mutations in those pathways. This sort of individualized and targeted approach would be expected to be highly efficacious in treating cancer and to have minimal side effects.
The rarity, changing properties and lack of key identifying features of circulating tumor cells have made their isolation and study challenging. We have developed our own instrument to isolate representative circulating tumor cells with high sensitivity, yield and purity. We now use it for our own basic and clinical research, and in collaboration with partners, to study the key mechanisms that underlie the spread of cancer in the body.
It is medically indicated to diagnose cancer based on the cells that spread the disease, and based on the molecular disease mechanisms that operate in those cells, since that opens for more effective treatment with lesser side effects.
EpCAM associates with endoplasmic reticulum aminopeptidase 2 (ERAP2) in breast cancer cells.
Biochem. Biophys. Res. Commun. 2013 Sep;439(2):203-8
Activation of neural and pluripotent stem cell signatures correlates with increased malignancy in human glioma.
PLoS ONE 2011 Mar;6(3):e18454
Uncoupling of the ERα regulated morphological phenotype from the cancer stem cell phenotype in human breast cancer cell lines.
Biochem. Biophys. Res. Commun. 2011 Feb;405(4):581-7
Juan Castro, Christer Ericsson, Peter Cashin and Haile Mahteme
Preliminary Finding: Detection of Circulating Cancer Cells in Blood from a Patient with Peritoneal Carcinomatosis Treated with Cytoreductive Surgery and Intraperitoneal Chemotherapy
Surgery : Current Research, 2012 Vol.2 Issue.3