التفاصيل البيبلوغرافية
| العنوان: |
Myeloma Microenvironmental TIMP1 Induces the Invasive Phenotype in Fibroblasts to Modulate Disease Progression |
| المؤلفون: |
Rei Ishihara, Tsukasa Oda, Yuki Murakami, Ikuko Matsumura, Saki Watanabe, Yuta Asao, Yuta Masuda, Nanami Gotoh, Tetsuhiro Kasamatsu, Hisashi Takei, Nobuhiko Kobayashi, Nobuo Sasaki, Takayuki Saitoh, Hirokazu Murakami, Hiroshi Handa |
| المصدر: |
International Journal of Molecular Sciences; Volume 24; Issue 3; Pages: 2216 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2023 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
multiple myeloma, tissue inhibitor of metalloproteinase, tumour microenvironment, fibroblast |
| جغرافية الموضوع: |
agris |
| الوصف: |
Tissue inhibitors of metalloproteinases (TIMPs) are endogenous matrix metalloproteinase inhibitors. TIMP1 is produced by cancer cells and has pleiotropic activities. However, its role and source in multiple myeloma (MM) are unclear. Here, we evaluated TIMP1 protein and mRNA levels in bone marrow (BM) plasma cells and assessed the effects of TIMP1 expression on fibroblast invasive capacity using three-dimensional spheroid cell invasion assays. TIMP1 mRNA and protein levels were elevated when patients progressed from monoclonal gammopathy of undetermined significance or smouldering myeloma to MM. Furthermore, TIMP1 levels decreased at complete response and TIMP1 protein levels increased with higher international staging. TIMP1 mRNA levels were markedly higher in extramedullary plasmacytoma and MM with t(4;14). Overall survival and post-progression survival were significantly lower in MM patients with high TIMP1 protein. Recombinant TIMP1 did not directly affect MM cells but enhanced the invasive capacity of fibroblasts; this effect was suppressed by treatment with anti-TIMP1 antibodies. Fibroblasts supported myeloma cell invasion and expansion in extracellular matrix. Overall, these results suggested that MM-derived TIMP1 induces the invasive phenotype in fibroblasts and is involved in disease progression. Further studies are required to elucidate the specific roles of TIMP1 in MM and facilitate the development of novel therapies targeting the TIMP1 pathway. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
Molecular Oncology; https://dx.doi.org/10.3390/ijms24032216Test |
| DOI: |
10.3390/ijms24032216 |
| الإتاحة: |
https://doi.org/10.3390/ijms24032216Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.1FF302F1 |
| قاعدة البيانات: |
BASE |
