Metformin enhances gefitinib efficacy by interfering with interactions between tumor-associated macrophages and head and neck squamous cell carcinoma cells,AbstractBackground
Tumor-associated macrophages (TAMs) play an important role in drug resistance in many tumors, including head and neck squamous cell carcinoma (HNSCC). However, how TAMs interact with HNSCC cells to induce drug resistance, especially under hypoxic conditions, is unclear. In this study, we investigated the mechanism of TAM-induced gefitinib resistance in HNSCC cells and sought for novel therapeutic strategies.
Methods
The effects of hypoxia-treated HNSCC cells on the migration and polarization of macrophages were analyzed. Recombinant cytokine proteins and neutralizing antibodies were used as controls. In addition, we assessed the cytotoxic effects of gefitinib on HNSCC cells treated with M2-type macrophage conditioned medium, and carried out a cytokine antibody array analysis, thereby revealing the key factor CCL15. The relationship between serum CCL15 expression levels and prognosis in HNSCC patients was analyzed. In addition, we performed bioinformatic analyses to pursue the mechanisms of CCL15-induced gefitinib resistance. Finally, metformin was used to evaluate the sensitizing effects of gefitinib treatment on HNSCC cells in vitro and in vivo.
Results
We found that HNSCC cells recruited macrophages by secreting VEGF and polarized the macrophages to the M2 phenotype through IL-6. Conversely, we found that M2-type TAMs promoted HNSCC cell resistance to gefitinib through paracrine CCL15 signaling. The serum CCL15 levels in HNSCC patients showed a significant correlation with patient prognosis. Furthermore, we found that M2-type TAMs could suppress the sensitivity of HNSCC cells to gefitinib through the CCL15-CCR1-NF-κB pathway. In addition, we found that metformin not only inhibited CCL15 expression in M2-type TAMs enhanced by hypoxia, but also suppressed CCR1 surface expression in HNSCC cells. Encouragingly, we found that metformin sensitized HNSCC cells to gefitinib treatment in vitro and in vivo.
Conclusions
Based on our data we conclude that we have identified a novel interaction between M2-type TAMs and HNSCC cells that contributes to gefitinib resistance. We also found that metformin inhibited the cross-talk between macrophages and tumor cells, thereby eliciting therapeutic effects both in vitro and in vivo.
|
ΩτοΡινοΛαρυγγολόγος Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,
Translate
Ετικέτες
Σάββατο 20 Ιουλίου 2019
Αναρτήθηκε από
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
στις
2:44 π.μ.
Ετικέτες
00302841026182,
00306932607174,
alsfakia@gmail.com,
Anapafseos 5 Agios Nikolaos 72100 Crete Greece,
Medicine by Alexandros G. Sfakianakis
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Αρχειοθήκη ιστολογίου
-
►
2023
(278)
- ► Φεβρουαρίου (139)
- ► Ιανουαρίου (139)
-
►
2022
(1962)
- ► Δεκεμβρίου (107)
- ► Σεπτεμβρίου (158)
- ► Φεβρουαρίου (165)
- ► Ιανουαρίου (163)
-
►
2021
(3614)
- ► Δεκεμβρίου (152)
- ► Σεπτεμβρίου (271)
- ► Φεβρουαρίου (64)
- ► Ιανουαρίου (357)
-
►
2020
(3279)
- ► Δεκεμβρίου (396)
- ► Σεπτεμβρίου (157)
- ► Φεβρουαρίου (382)
- ► Ιανουαρίου (84)
-
▼
2019
(11718)
- ► Δεκεμβρίου (265)
- ► Σεπτεμβρίου (545)
-
▼
Ιουλίου
(1727)
- Viruses, Vol. 11, Pages 701: Metagenomic N...
- Vaccines, Vol. 7, Pages 77: Nanobodies that Neutr...
- Antibiotic and Pesticides Residues in Breast Milk
- Social Sciences, Vol. 8, Pages 229: The Street-Wi...
- Psych, Vol. 1, Pages 429-430: Expression of Conce...
- Microorganisms, Vol. 7, Pages 230: Contras...
- Medicina, Vol. 55, Pages 423: Handheld Ult...
- JCM, Vol. 8, Pages 1144: Shock Index Predi...
- Humanities, Vol. 8, Pages 130: The Composi...
- Children, Vol. 6, Pages 89: Emerging Topics in Ca...
- Cancers, Vol. 11, Pages 1091: Glioblastoma...
- Impact of skeletal muscle mass volume on surgica...
- A method using the cephalic vein for superdraina...
- Direct muscle neurotization with long acellular ...
- Allergy, Asthma , Immunology
- CranioMaxillofacial Surgery
- Neuroradiology/Head and Neck ImagingOriginal Res...
- Systems approach reveals photosensitivity and P...
- NeuroOncology
- Griseofulvin versus Terbinafine for pediatric Ti...
- Identification of Cryptococcus Antigen in HIV‐po...
- Epidemiology and Management Burden of Invasive F...
- Phaeohyphomycosis caused by Phialophora american...
- MicrosurgeryEarly View Online Version of Recor...
- Chondro-Osseous Respiratory Epithelial Adenoma...
- Otolaryngology
- Adult-Type Rhabdomyoma of the Omohyoid Muscle ...
- Thyroglossal Duct Cyst Carcinoma in a Young Fe...
- Case Reports in Otolaryngology Volume 2019, Arti...
- Lung Perfusion Scintigraphy in Eisenmenger Syndr...
- Case Reports in Otolaryngology
- Otology & Neurotology
- Hunger-Activated AgRP Neurons Inhibit MPOA Neur...
- Development of a delayed-release nutrient for appe...
- Neoadjuvant BRAF‐targeted therapy in regionally ...
- Discoidin domain receptors: A promising target i...
- Self-seeding circulating tumor cells promote th...
- Necrosis Rather Than Apoptosis is The Dominant f...
- Magician's Corner: How to Start Lear...
- Impact of Long Wavelength Ultraviolet A1 and Vis...
- Method for Measurements of Terrestrial Ultravio...
- Unusually complicated course of a common disease...
- Lead poisoning has been described in older childre...
- Teaching Topic Immediate Transfusion in Africa...
- INTERACTIVE MEDICAL CASE
- Weighing the Risks and Rewards of Peanut Oral...
- Buried bumper syndrome (BBS) is one of the uncommo...
- GASTROENTEROLOGY ENDOSCOPY: NOT JUST A PROCEDURA...
- Health Physics
- Techniques in Shoulder & Elbow Surgery
- Primer on Precision Medicine for Complex Chronic...
- Clinical and Translational Gastroenterology
- Technological Pedagogical and Content Knowledge ...
- Intraoperative Placement of Paravertebral Cathet...
- Heterogeneity of human pancreatic islet isolatio...
- Anaesthesia
- Academic Medicine
- Menopause
- Clinical Orthopaedics and Related Research(R)
- pH-sensitive anti-CTLA4 antibodies: yes to effi...
- Therapeutics
- American Journal of Therapeutics
- FULL MOON > AUGUST - We have the Algonquin Indians...
- Medicine by Alexandros G. Sfakianakis,Anapafseos 5...
- Pediatric Radiology
- Obesity Surgery
- Pediatric Orthopaedics
- Rheumatology
- Anaesthesiology
- Cardiovascular Medicine
- Medicine by Alexandros G. Sfakianakis,Anapafseos 5...
- Trauma and Acute Care Surgery
- Cancer Research and Clinical Oncology
- Endocrine
- Medicine by Alexandros G. Sfakianakis,Anapafseos 5...
- Hypertension
- Angiogenesis
- Musculoskeletal Surgery
- Physiological Sciences
- Cardiology
- Gastroenterology
- Medicine by Alexandros G. Sfakianakis,Anapafseos 5...
- Update on treatment options for blast-induced he...
- Triglycerides and endothelial function: molecula...
- Neuropsychology as a Method of Diagnosis and Tre...
- Combination of laser microdissection, 2D-DIGE an...
- Plasma lipoproteome in Alzheimer’s disease: a p...
- Validation of a novel model for the early dete...
- Journal of the European Academy of Dermatology a...
- ► Φεβρουαρίου (1143)
- ► Ιανουαρίου (744)
-
►
2017
(2)
- ► Φεβρουαρίου (1)
- ► Ιανουαρίου (1)
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου