Intracellular collagen degradation mediated by uPARAP/Endo180 is a major pathway of extracellular matrix turnover during malignancy

TY - JOUR

T1 - Intracellular collagen degradation mediated by uPARAP/Endo180 is a major pathway of extracellular matrix turnover during malignancy

AU - Curino, Alejandro C

AU - Engelholm, Lars H

AU - Yamada, Susan S

AU - Holmbeck, Kenn

AU - Lund, Leif R

AU - Molinolo, Alfredo

AU - Behrendt, Niels

AU - Nielsen, Boye Schnack

AU - Bugge, Thomas H.

PY - 2005/6/20

Y1 - 2005/6/20

N2 - We recently reported that uPARAP/Endo180 can mediate the cellular uptake and lysosomal degradation of collagen by cultured fibroblasts. Here, we show that uPARAP/Endo180 has a key role in the degradation of collagen during mammary carcinoma progression. In the normal murine mammary gland, uPARAP/Endo180 is widely expressed in periductal fibroblast-like mesenchymal cells that line mammary epithelial cells. This pattern of uPARAP/Endo180 expression is preserved during polyomavirus middle T-induced mammary carcinogenesis, with strong uPARAP/Endo180 expression by mesenchymal cells embedded within the collagenous stroma surrounding nests of uPARAP/Endo180-negative tumor cells. Genetic ablation of uPARAP/Endo180 impaired collagen turnover that is critical to tumor expansion, as evidenced by the abrogation of cellular collagen uptake, tumor fibrosis, and blunted tumor growth. These studies identify uPARAP/Endo180 as a key mediator of collagen turnover in a pathophysiological context.

AB - We recently reported that uPARAP/Endo180 can mediate the cellular uptake and lysosomal degradation of collagen by cultured fibroblasts. Here, we show that uPARAP/Endo180 has a key role in the degradation of collagen during mammary carcinoma progression. In the normal murine mammary gland, uPARAP/Endo180 is widely expressed in periductal fibroblast-like mesenchymal cells that line mammary epithelial cells. This pattern of uPARAP/Endo180 expression is preserved during polyomavirus middle T-induced mammary carcinogenesis, with strong uPARAP/Endo180 expression by mesenchymal cells embedded within the collagenous stroma surrounding nests of uPARAP/Endo180-negative tumor cells. Genetic ablation of uPARAP/Endo180 impaired collagen turnover that is critical to tumor expansion, as evidenced by the abrogation of cellular collagen uptake, tumor fibrosis, and blunted tumor growth. These studies identify uPARAP/Endo180 as a key mediator of collagen turnover in a pathophysiological context.

KW - Animals

KW - Carcinoma

KW - Cell Transformation, Neoplastic

KW - Cells, Cultured

KW - Collagen

KW - Disease Models, Animal

KW - Extracellular Matrix

KW - Female

KW - Mammary Glands, Animal

KW - Mammary Neoplasms, Experimental

KW - Membrane Glycoproteins

KW - Mesoderm

KW - Mice

KW - Mice, Knockout

KW - Microscopy, Electron, Transmission

KW - Molecular Sequence Data

KW - Neoplasm Invasiveness

KW - Polyomavirus

KW - Receptors, Cell Surface

KW - Stromal Cells

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Research Support, U.S. Gov't, Non-P.H.S.

U2 - 10.1083/jcb.200411153

DO - 10.1083/jcb.200411153

M3 - Journal article

C2 - 15967816

SN - 0021-9525

VL - 169

SP - 977

EP - 985

JO - Journal of Cell Biology

JF - Journal of Cell Biology

IS - 6

ER -