Cell Adhesion and Cancer Progression:
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, a protein mostly expressed by ductal carcinomas. E-cadherin is a key component of adherens junctions, master regulators in the maintenance of tissue integrity.
Dysfunction of epithelial adhesion complexes is strongly related to cancer invasion and metastasis.
We are using mouse and human models of breast cancer to study metastatic breast cancer. We are aiming at understanding the malignant behaviour of invasive cancer, starting from cell adhesion point-of-view We aim to identify the molecular cues that are triggered upon loss of cadherin-based cell-cell adhesions, integrin-dependent ECM interactions, and how they impact tumor progression through modulation of the cytoskeleton. For these studies we are mainly using 2 and 3-dimensional culture systems 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.
Our studies are sponsored by KWF, NWO, STW, BCN 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, a protein mostly expressed by ductal carcinomas. E-cadherin is a key component of adherens junctions, master regulators in the maintenance of tissue integrity.
Dysfunction of epithelial adhesion complexes is strongly related to cancer invasion and metastasis.
We are using mouse and human models of breast cancer to study metastatic breast cancer. We are aiming at understanding the malignant behaviour of invasive cancer, starting from cell adhesion point-of-view We aim to identify the molecular cues that are triggered upon loss of cadherin-based cell-cell adhesions, integrin-dependent ECM interactions, and how they impact tumor progression through modulation of the cytoskeleton. For these studies we are mainly using 2 and 3-dimensional culture systems 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.
Our studies are sponsored by KWF, NWO, STW, BCN and the European Union H2020 program.
