Extracellular matrix components in breast cancer progression and metastasis.
The extracellular matrix (ECM) is composed of highly variable and dynamic components that regulate cell behavior. The protein composition and physical properties of the ECM govern cell fate through biochemical and biomechanical mechanisms. This requires a carefully orchestrated and thorough regulation considering that a disturbed ECM can have serious consequences and lead to pathological conditions like cancer. In breast cancer, many ECM proteins are significantly deregulated and specific matrix components promote tumor progression and metastatic spread. Intriguingly, several ECM proteins that are associated with breast cancer development, overlap substantially with a group of ECM proteins induced during the state of tissue remodeling such as mammary gland involution. Fibrillar collagens, fibronectin, hyaluronan and matricellular proteins are matrix components that are common to both involution and cancer. Moreover, some of these proteins have in recent years been identified as important constituents of metastatic niches in breast cancer. In addition, specific ECM molecules, their receptors or enzymatic modifiers are significantly involved in resistance to therapeutic intervention. Further analysis of these ECM proteins and the downstream ECM mediated signaling pathways may provide a range of possibilities to identify druggable targets against advanced breast cancer.
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany; Divison of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany. Electronic address: t.oskarsson@dkfz.de.
Thordur
T
Oskarsson
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008321:Mammary Glands, Animal / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D017382:Reactive Oxygen Species
Extracellular matrix; Mammary gland involution; Metastatic breast cancer; Metastatic niche; Therapy resistance; Tissue remodeling