Cell Adhesion and Cancer Progression:
Models, Mechanisms and Options for Intervention
Models, Mechanisms and Options for Intervention
Focus:
Breast cancer results in approximately half a million deaths on an annual basis. In breast cancer, loss of cell-cell adhesion is a decisive event in determining breast cancer types. Lobular carcinoma, a unique breast cancer type, is caused by loss of E-cadherin.
E-cadherin is the key component of adherens junctions, master regulators in the maintenance of tissue integrity. Dysfunction of epithelial adhesion complexes is strongly related to invasion and metastasis in several carcinomas.
We are using mouse and human models of breast cancer to study metastatic breast cancer. We aim at understanding the malignant behaviour of invasive cancer, starting from a cell adhesion point-of-view and identifying the molecular cues that are triggered upon loss of cadherin-based cell- adhesions. For these studies we are mainly using 2 and 3-dimensional culture systems using cell lines and primary patient samples combined with genetics, biochemistry and fluorescence microscopy.
For in vivo validation purposes, we have developed robust tumor progression and metastasis assays, based on orthotopic transplantation and bioluminescence imaging of luciferase-expressing cell lines, tumors and primary conditional and wild-type mouse mammary epithelial cells.
These assays are employed to validate genes that are nominated as novel regulators of tumor initiation and progression. To translate our findings, we are preforming preclinical intervention trials in mice with the ultimate goal to implement new interventions to improve cancer treatment. We have recently expanded our interests to Head & Neck Oral Squamous Cell Carcinoma (OSCC).
Our studies are sponsored by KWF, Health~Holland, NWO, STW, Breast Cancer Now, and the European Union H2020 program.
Breast cancer results in approximately half a million deaths on an annual basis. In breast cancer, loss of cell-cell adhesion is a decisive event in determining breast cancer types. Lobular carcinoma, a unique breast cancer type, is caused by loss of E-cadherin.
E-cadherin is the key component of adherens junctions, master regulators in the maintenance of tissue integrity. Dysfunction of epithelial adhesion complexes is strongly related to invasion and metastasis in several carcinomas.
We are using mouse and human models of breast cancer to study metastatic breast cancer. We aim at understanding the malignant behaviour of invasive cancer, starting from a cell adhesion point-of-view and identifying the molecular cues that are triggered upon loss of cadherin-based cell- adhesions. For these studies we are mainly using 2 and 3-dimensional culture systems using cell lines and primary patient samples combined with genetics, biochemistry and fluorescence microscopy.
For in vivo validation purposes, we have developed robust tumor progression and metastasis assays, based on orthotopic transplantation and bioluminescence imaging of luciferase-expressing cell lines, tumors and primary conditional and wild-type mouse mammary epithelial cells.
These assays are employed to validate genes that are nominated as novel regulators of tumor initiation and progression. To translate our findings, we are preforming preclinical intervention trials in mice with the ultimate goal to implement new interventions to improve cancer treatment. We have recently expanded our interests to Head & Neck Oral Squamous Cell Carcinoma (OSCC).
Our studies are sponsored by KWF, Health~Holland, NWO, STW, Breast Cancer Now, and the European Union H2020 program.
