Normal mammary epithelial cells promote carcinoma basement membrane invasion by inducing microtubule-rich protrusions.
Recent work suggests that the dissemination of tumor cells may occur in parallel with, and even preceed, tumor growth. The mechanism for this early invasion is largely unknown. Here, we find that mammary epithelial cells (MECs) induce neighboring breast carcinoma cells (BCCs) to cross the basement membrane by secreting soluble laminin. Laminin continuously produced by MECs induce long membrane cellular protrusions in BCCs that promote their contractility and invasion into the surrounding matrix. These protrusions depend on microtubule bundles assembled de novo through laminin-integrin β1 signaling. These results describe how non-cancerous MECs can actively participate in the invasive process of BCCs.
Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Meng-Horng
MH
Lee
Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Pei-Hsun
PH
Wu
Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Daniele
D
Gilkes
Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Ivie
I
Aifuwa
Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Departments of Pathology and Oncology, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.|Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
Denis
D
Wirtz
D001485:Basement Membrane / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D002460:Cell Line; D002465:Cell Movement; D022081:Cell Surface Extensions / Q000378:metabolism* / Q000473:pathology; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D007797:Laminin / Q000378:metabolism*; D042361:Mammary Glands, Human / Q000378:metabolism* / Q000473:pathology; D008870:Microtubules / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D019899:Paracrine Communication; D010641:Phenotype; D011379:Prognosis; D015398:Signal Transduction; D012995:Solubility; D013997:Time Factors; D014162:Transfection
D019012:Integrin beta1; D007797:Laminin
cancer invasion; cell-cell interaction; laminin; microtubule; protrusion