IGFBP3 inhibits tumor growth and invasion of lung cancer cells and is associated with improved survival in lung cancer patients
The insulin-like growth factor (IGF)-pathway is involved in tumor cell proliferation, metastasis, and survival. We aimed to find out what effects IGF binding protein 3 (IGFBP3) exerted on H1299 lung cancer (LC) cells in terms of tumor growth and invasion and whether IGFBP3 was associated with clinic...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Translational Oncology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S193652332200225X |
| _version_ | 1811295068211904512 |
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| author | Hartmut Kuhn Armin Frille Marie Anna Petersen Jonas Oberhuber-Kurth Lukas Hofmann Albrecht Gläser Sabine Taubenheim Sabine Klagges Sebastian Kraemer Johannes Broschewitz Maximilian von Laffert Hubert Wirtz |
| author_facet | Hartmut Kuhn Armin Frille Marie Anna Petersen Jonas Oberhuber-Kurth Lukas Hofmann Albrecht Gläser Sabine Taubenheim Sabine Klagges Sebastian Kraemer Johannes Broschewitz Maximilian von Laffert Hubert Wirtz |
| author_sort | Hartmut Kuhn |
| collection | DOAJ |
| description | The insulin-like growth factor (IGF)-pathway is involved in tumor cell proliferation, metastasis, and survival. We aimed to find out what effects IGF binding protein 3 (IGFBP3) exerted on H1299 lung cancer (LC) cells in terms of tumor growth and invasion and whether IGFBP3 was associated with clinical and pathological parameters in a prospective cohort of LC patients. H1299 cells were transfected with an IGFBP3-expressing vector. Its influence on apoptosis induction via flow cytometry annexin V FITC assay, cell proliferation in 2D and 3D cell culture, and invasion were examined. Expression of several matrix metalloproteinases (MMPs) and inhibitors (TIMP-1) were also investigated in IGFBP3-transfected LC cells. Further, data on LC patients (n = 131), tumor characteristics, and survival were prospectively collected and correlated with IGFBP3 plasma levels. IGFBP3 did not influence apoptosis induction and 2D cell proliferation. However, both spheroid growth (3D proliferation) and invasion of IGFBP3-transfected cells planted in an extracellular matrix-based gel were significantly inhibited. IGFBP3 inhibited MMP-1 release, and the total MMP activity. In LC patients, higher IGFBP3 plasma levels correlated with both lower clinical tumor stage, grading, Ki-67 staining, and the absence of necrosis (P < 0.05, respectively). Increased IGFBP3 plasma levels were associated with improved overall survival (hazard ratio 0.37, P = 0.01). In conclusion, overexpressed IGFBP3 in a LC cell line inhibited tumor growth and invasion. Translating from bench to bedside, investigation of clinicopathological parameters confirmed these experimental results showing that higher IGFBP3 plasma levels were associated with less aggressive tumor growth, reduced tumor spread, and improved survival of LC patients. |
| first_indexed | 2024-04-13T05:26:50Z |
| format | Article |
| id | doaj.art-ab51f75008454de5b1b889c501a93717 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-04-13T05:26:50Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-ab51f75008454de5b1b889c501a937172022-12-22T03:00:34ZengElsevierTranslational Oncology1936-52332023-01-0127101566IGFBP3 inhibits tumor growth and invasion of lung cancer cells and is associated with improved survival in lung cancer patientsHartmut Kuhn0Armin Frille1Marie Anna Petersen2Jonas Oberhuber-Kurth3Lukas Hofmann4Albrecht Gläser5Sabine Taubenheim6Sabine Klagges7Sebastian Kraemer8Johannes Broschewitz9Maximilian von Laffert10Hubert Wirtz11Department of Respiratory Medicine, University Hospital Leipzig, Liebigstraße 21, Leipzig 04103, Germany; Corresponding author.Department of Respiratory Medicine, University Hospital Leipzig, Liebigstraße 21, Leipzig 04103, Germany; Integrated Research and Treatment Center (IFB) Adiposity Diseases, University Medical Center Leipzig, Leipzig, GermanyDepartment of Respiratory Medicine, University Hospital Leipzig, Liebigstraße 21, Leipzig 04103, GermanyDepartment of Respiratory Medicine, University Hospital Leipzig, Liebigstraße 21, Leipzig 04103, GermanyDepartment of Respiratory Medicine, University Hospital Leipzig, Liebigstraße 21, Leipzig 04103, GermanyClinical Cancer Registry Leipzig, University Medical Center Leipzig, GermanyClinical Cancer Registry Leipzig, University Medical Center Leipzig, GermanyClinical Cancer Registry Leipzig, University Medical Center Leipzig, GermanyDepartment of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, GermanyDepartment of Thoracic Surgery, Medical Centre Bremen-Ost, Bremen, GermanyInstitute of Pathology, University Hospital Leipzig, GermanyDepartment of Respiratory Medicine, University Hospital Leipzig, Liebigstraße 21, Leipzig 04103, GermanyThe insulin-like growth factor (IGF)-pathway is involved in tumor cell proliferation, metastasis, and survival. We aimed to find out what effects IGF binding protein 3 (IGFBP3) exerted on H1299 lung cancer (LC) cells in terms of tumor growth and invasion and whether IGFBP3 was associated with clinical and pathological parameters in a prospective cohort of LC patients. H1299 cells were transfected with an IGFBP3-expressing vector. Its influence on apoptosis induction via flow cytometry annexin V FITC assay, cell proliferation in 2D and 3D cell culture, and invasion were examined. Expression of several matrix metalloproteinases (MMPs) and inhibitors (TIMP-1) were also investigated in IGFBP3-transfected LC cells. Further, data on LC patients (n = 131), tumor characteristics, and survival were prospectively collected and correlated with IGFBP3 plasma levels. IGFBP3 did not influence apoptosis induction and 2D cell proliferation. However, both spheroid growth (3D proliferation) and invasion of IGFBP3-transfected cells planted in an extracellular matrix-based gel were significantly inhibited. IGFBP3 inhibited MMP-1 release, and the total MMP activity. In LC patients, higher IGFBP3 plasma levels correlated with both lower clinical tumor stage, grading, Ki-67 staining, and the absence of necrosis (P < 0.05, respectively). Increased IGFBP3 plasma levels were associated with improved overall survival (hazard ratio 0.37, P = 0.01). In conclusion, overexpressed IGFBP3 in a LC cell line inhibited tumor growth and invasion. Translating from bench to bedside, investigation of clinicopathological parameters confirmed these experimental results showing that higher IGFBP3 plasma levels were associated with less aggressive tumor growth, reduced tumor spread, and improved survival of LC patients.http://www.sciencedirect.com/science/article/pii/S193652332200225X |
| spellingShingle | Hartmut Kuhn Armin Frille Marie Anna Petersen Jonas Oberhuber-Kurth Lukas Hofmann Albrecht Gläser Sabine Taubenheim Sabine Klagges Sebastian Kraemer Johannes Broschewitz Maximilian von Laffert Hubert Wirtz IGFBP3 inhibits tumor growth and invasion of lung cancer cells and is associated with improved survival in lung cancer patients Translational Oncology |
| title | IGFBP3 inhibits tumor growth and invasion of lung cancer cells and is associated with improved survival in lung cancer patients |
| title_full | IGFBP3 inhibits tumor growth and invasion of lung cancer cells and is associated with improved survival in lung cancer patients |
| title_fullStr | IGFBP3 inhibits tumor growth and invasion of lung cancer cells and is associated with improved survival in lung cancer patients |
| title_full_unstemmed | IGFBP3 inhibits tumor growth and invasion of lung cancer cells and is associated with improved survival in lung cancer patients |
| title_short | IGFBP3 inhibits tumor growth and invasion of lung cancer cells and is associated with improved survival in lung cancer patients |
| title_sort | igfbp3 inhibits tumor growth and invasion of lung cancer cells and is associated with improved survival in lung cancer patients |
| url | http://www.sciencedirect.com/science/article/pii/S193652332200225X |
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