Discoidin domain receptor 1 (DDR1) ablation promotes tissue fibrosis and hypoxia to induce aggressive basal-like breast cancers [Research Papers]

Publication Date:
2018-03-06
Publisher:
Cold Spring Harbor Laboratory Press
Print ISSN:
0890-9369
Topics:
Biology
Published by:
http://www.cshlpress.com/
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autor Takai, K., Drain, A. P., Lawson, D. A., Littlepage, L. E., Karpuj, M., Kessenbrock, K., Le, A., Inoue, K., Weaver, V. M., Werb, Z.
beschreibung The discoidin domain receptor 1 (DDR1) is overexpressed in breast carcinoma cells. Low DDR1 expression is associated with worse relapse-free survival, reflecting its controversial role in cancer progression. We detected DDR1 on luminal cells but not on myoepithelial cells of DDR1 +/+ mice. We found that DDR1 loss compromises cell adhesion, consistent with data that older DDR1 –/– mammary glands had more basal/myoepithelial cells. Basal cells isolated from older mice exerted higher traction forces than the luminal cells, in agreement with increased mammary branches observed in older DDR1 –/– mice and higher branching by their isolated organoids. When we crossed DDR1 –/– mice with MMTV-PyMT mice, the PyMT/DDR1 –/– mammary tumors grew faster and had increased epithelial tension and matricellular fibrosis with a more basal phenotype and increased lung metastases. DDR1 deletion induced basal differentiation of CD90 + CD24 + cancer cells, and the increase in basal cells correlated with tumor cell mitoses. K14 + basal cells, including K8 + K14 + cells, were increased adjacent to necrotic fields. These data suggest that the absence of DDR1 provides a growth and adhesion advantage that favors the expansion of basal cells, potentiates fibrosis, and enhances necrosis/hypoxia and basal differentiation of transformed cells to increase their aggression and metastatic potential.
citation_standardnr 6185813
datenlieferant ipn_articles
feed_id 1644
feed_publisher Cold Spring Harbor Laboratory Press
feed_publisher_url http://www.cshlpress.com/
insertion_date 2018-03-06
journalissn 0890-9369
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher Cold Spring Harbor Laboratory Press
quelle Genes & Development
relation http://genesdev.cshlp.org/cgi/content/short/32/3-4/244?rss=1
search_space articles
shingle_author_1 Takai, K., Drain, A. P., Lawson, D. A., Littlepage, L. E., Karpuj, M., Kessenbrock, K., Le, A., Inoue, K., Weaver, V. M., Werb, Z.
shingle_author_2 Takai, K., Drain, A. P., Lawson, D. A., Littlepage, L. E., Karpuj, M., Kessenbrock, K., Le, A., Inoue, K., Weaver, V. M., Werb, Z.
shingle_author_3 Takai, K., Drain, A. P., Lawson, D. A., Littlepage, L. E., Karpuj, M., Kessenbrock, K., Le, A., Inoue, K., Weaver, V. M., Werb, Z.
shingle_author_4 Takai, K., Drain, A. P., Lawson, D. A., Littlepage, L. E., Karpuj, M., Kessenbrock, K., Le, A., Inoue, K., Weaver, V. M., Werb, Z.
shingle_catch_all_1 Discoidin domain receptor 1 (DDR1) ablation promotes tissue fibrosis and hypoxia to induce aggressive basal-like breast cancers [Research Papers]
The discoidin domain receptor 1 (DDR1) is overexpressed in breast carcinoma cells. Low DDR1 expression is associated with worse relapse-free survival, reflecting its controversial role in cancer progression. We detected DDR1 on luminal cells but not on myoepithelial cells of DDR1 +/+ mice. We found that DDR1 loss compromises cell adhesion, consistent with data that older DDR1 –/– mammary glands had more basal/myoepithelial cells. Basal cells isolated from older mice exerted higher traction forces than the luminal cells, in agreement with increased mammary branches observed in older DDR1 –/– mice and higher branching by their isolated organoids. When we crossed DDR1 –/– mice with MMTV-PyMT mice, the PyMT/DDR1 –/– mammary tumors grew faster and had increased epithelial tension and matricellular fibrosis with a more basal phenotype and increased lung metastases. DDR1 deletion induced basal differentiation of CD90 + CD24 + cancer cells, and the increase in basal cells correlated with tumor cell mitoses. K14 + basal cells, including K8 + K14 + cells, were increased adjacent to necrotic fields. These data suggest that the absence of DDR1 provides a growth and adhesion advantage that favors the expansion of basal cells, potentiates fibrosis, and enhances necrosis/hypoxia and basal differentiation of transformed cells to increase their aggression and metastatic potential.
Takai, K., Drain, A. P., Lawson, D. A., Littlepage, L. E., Karpuj, M., Kessenbrock, K., Le, A., Inoue, K., Weaver, V. M., Werb, Z.
Cold Spring Harbor Laboratory Press
0890-9369
08909369
shingle_catch_all_2 Discoidin domain receptor 1 (DDR1) ablation promotes tissue fibrosis and hypoxia to induce aggressive basal-like breast cancers [Research Papers]
The discoidin domain receptor 1 (DDR1) is overexpressed in breast carcinoma cells. Low DDR1 expression is associated with worse relapse-free survival, reflecting its controversial role in cancer progression. We detected DDR1 on luminal cells but not on myoepithelial cells of DDR1 +/+ mice. We found that DDR1 loss compromises cell adhesion, consistent with data that older DDR1 –/– mammary glands had more basal/myoepithelial cells. Basal cells isolated from older mice exerted higher traction forces than the luminal cells, in agreement with increased mammary branches observed in older DDR1 –/– mice and higher branching by their isolated organoids. When we crossed DDR1 –/– mice with MMTV-PyMT mice, the PyMT/DDR1 –/– mammary tumors grew faster and had increased epithelial tension and matricellular fibrosis with a more basal phenotype and increased lung metastases. DDR1 deletion induced basal differentiation of CD90 + CD24 + cancer cells, and the increase in basal cells correlated with tumor cell mitoses. K14 + basal cells, including K8 + K14 + cells, were increased adjacent to necrotic fields. These data suggest that the absence of DDR1 provides a growth and adhesion advantage that favors the expansion of basal cells, potentiates fibrosis, and enhances necrosis/hypoxia and basal differentiation of transformed cells to increase their aggression and metastatic potential.
Takai, K., Drain, A. P., Lawson, D. A., Littlepage, L. E., Karpuj, M., Kessenbrock, K., Le, A., Inoue, K., Weaver, V. M., Werb, Z.
Cold Spring Harbor Laboratory Press
0890-9369
08909369
shingle_catch_all_3 Discoidin domain receptor 1 (DDR1) ablation promotes tissue fibrosis and hypoxia to induce aggressive basal-like breast cancers [Research Papers]
The discoidin domain receptor 1 (DDR1) is overexpressed in breast carcinoma cells. Low DDR1 expression is associated with worse relapse-free survival, reflecting its controversial role in cancer progression. We detected DDR1 on luminal cells but not on myoepithelial cells of DDR1 +/+ mice. We found that DDR1 loss compromises cell adhesion, consistent with data that older DDR1 –/– mammary glands had more basal/myoepithelial cells. Basal cells isolated from older mice exerted higher traction forces than the luminal cells, in agreement with increased mammary branches observed in older DDR1 –/– mice and higher branching by their isolated organoids. When we crossed DDR1 –/– mice with MMTV-PyMT mice, the PyMT/DDR1 –/– mammary tumors grew faster and had increased epithelial tension and matricellular fibrosis with a more basal phenotype and increased lung metastases. DDR1 deletion induced basal differentiation of CD90 + CD24 + cancer cells, and the increase in basal cells correlated with tumor cell mitoses. K14 + basal cells, including K8 + K14 + cells, were increased adjacent to necrotic fields. These data suggest that the absence of DDR1 provides a growth and adhesion advantage that favors the expansion of basal cells, potentiates fibrosis, and enhances necrosis/hypoxia and basal differentiation of transformed cells to increase their aggression and metastatic potential.
Takai, K., Drain, A. P., Lawson, D. A., Littlepage, L. E., Karpuj, M., Kessenbrock, K., Le, A., Inoue, K., Weaver, V. M., Werb, Z.
Cold Spring Harbor Laboratory Press
0890-9369
08909369
shingle_catch_all_4 Discoidin domain receptor 1 (DDR1) ablation promotes tissue fibrosis and hypoxia to induce aggressive basal-like breast cancers [Research Papers]
The discoidin domain receptor 1 (DDR1) is overexpressed in breast carcinoma cells. Low DDR1 expression is associated with worse relapse-free survival, reflecting its controversial role in cancer progression. We detected DDR1 on luminal cells but not on myoepithelial cells of DDR1 +/+ mice. We found that DDR1 loss compromises cell adhesion, consistent with data that older DDR1 –/– mammary glands had more basal/myoepithelial cells. Basal cells isolated from older mice exerted higher traction forces than the luminal cells, in agreement with increased mammary branches observed in older DDR1 –/– mice and higher branching by their isolated organoids. When we crossed DDR1 –/– mice with MMTV-PyMT mice, the PyMT/DDR1 –/– mammary tumors grew faster and had increased epithelial tension and matricellular fibrosis with a more basal phenotype and increased lung metastases. DDR1 deletion induced basal differentiation of CD90 + CD24 + cancer cells, and the increase in basal cells correlated with tumor cell mitoses. K14 + basal cells, including K8 + K14 + cells, were increased adjacent to necrotic fields. These data suggest that the absence of DDR1 provides a growth and adhesion advantage that favors the expansion of basal cells, potentiates fibrosis, and enhances necrosis/hypoxia and basal differentiation of transformed cells to increase their aggression and metastatic potential.
Takai, K., Drain, A. P., Lawson, D. A., Littlepage, L. E., Karpuj, M., Kessenbrock, K., Le, A., Inoue, K., Weaver, V. M., Werb, Z.
Cold Spring Harbor Laboratory Press
0890-9369
08909369
shingle_title_1 Discoidin domain receptor 1 (DDR1) ablation promotes tissue fibrosis and hypoxia to induce aggressive basal-like breast cancers [Research Papers]
shingle_title_2 Discoidin domain receptor 1 (DDR1) ablation promotes tissue fibrosis and hypoxia to induce aggressive basal-like breast cancers [Research Papers]
shingle_title_3 Discoidin domain receptor 1 (DDR1) ablation promotes tissue fibrosis and hypoxia to induce aggressive basal-like breast cancers [Research Papers]
shingle_title_4 Discoidin domain receptor 1 (DDR1) ablation promotes tissue fibrosis and hypoxia to induce aggressive basal-like breast cancers [Research Papers]
timestamp 2025-06-30T23:33:10.395Z
titel Discoidin domain receptor 1 (DDR1) ablation promotes tissue fibrosis and hypoxia to induce aggressive basal-like breast cancers [Research Papers]
titel_suche Discoidin domain receptor 1 (DDR1) ablation promotes tissue fibrosis and hypoxia to induce aggressive basal-like breast cancers [Research Papers]
topic W
uid ipn_articles_6185813