Loss of nidogen-1 causes lung basement membrane defects and increased metastasis.

ABSTRACT: Metastasis is the most common cause of cancer patient deaths. It is a complex process strongly influenced by the extracellular matrix (ECM). A mass spectrometry analysis comparing ECM proteins from healthy mouse lungs versus metastatic lungs has previously been performed, and the basement membrane (BM) component nidogen-1 has been identified to be one of the most downregulated ECM proteins in metastatic lungs. Here, we investigated the role of stromal cell-derived nidogen-1 in metastasis. We found that nidogen-1 is expressed by fibroblasts but not cancer cells, and nidogen-1 is downregulated in breast tumors compared to healthy mammary gland. Using the HCmel12 melanoma model, we found that loss of stromal nidogen-1 causes increased lung metastasis. Using electron microscopy, we found that

SUBMITTER: Xia T 

PROVIDER: S-EPMC12571852 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature