IL-8 from CD248-expressing cancer-associated fibroblasts generates cisplatin resistance in non-small cell lung cancer.

Chemotherapy-resistant non-small cell lung cancer (NSCLC) presents a substantial barrier to effective care. It is still unclear how cancer-associated fibroblasts (CAFs) contribute to NSCLC resistance to chemotherapy. Here, we found that CD248+ CAFs released IL-8 in NSCLC, which, in turn, enhanced the cisplatin (CDDP) IC50 in A549 and NCI-H460 while decreasing the apoptotic percentage of A549 and NCI-H460 in vitro. The CD248+ CAFs-based IL-8 secretion induced NSCLC chemoresistance by stimulating nuclear factor kappa B (NF-κB) and elevating ATP-binding cassette transporter B1 (ABCB1). We also revealed that the CD248+ CAFs-based IL-8 release enhanced cisplatin chemoresistance in NSCLC mouse models in vivo. Relative to wild-type control mice, the CD248 conditional knockout mice exhibited significant reduction of IL-8 secretion, which, in turn, enhanced the therapeutic efficacy of cisplatin in vivo. In summary, our study identified CD248 activates the NF-κB axis, which, consecutively induces the CAFs-based secretion of IL-8, which promotes NSCLC chemoresistance. This report highlights a potential new approach to enhancing the chemotherapeutic potential of NSCLC-treating cisplatin.

Mussel-Inspired Wet-Adhesive Multifunctional Organohydrogel with Extreme Environmental Tolerance for Wearable Strain Sensor.

As a flexible artificial material, the conductive hydrogel has broad application prospects in flexible wearable electronics, soft robotics, and biomedical monitoring. However, traditional hydrogels still face many challenges, such as long-term stability, availability in extreme environments, and long-lasting adhesion to the skin surface under sweaty or humid conditions. To circumvent the above issues, one kind of ionic conductive hydrogel was prepared by a simple one-pot method that dissolved chitosan (CS), 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS), tannic acid (TA), and 2-methoxy-ethyl acrylate (MEA) into dimethyl sulfoxide (DMSO)/H2O solvent. The resulting hydrogel showed excellent tensile properties (1440%), extreme environmental tolerance (-40-60 °C), adhesion (72 KPa at porcine skin), ionic conductivity (0.87 S m-1), and high-efficiency antibacterial property. Furthermore, the produced organohydrogel strain sensor exhibited high strain sensitivity (GF = 4.07), excellent signal sensing capabilities (human joint movement, microexpression, and sound signals), and long-term cyclic stability (400 cycles). Looking beyond, this work provides a simple and promising strategy for using hydrogel sensors in extreme environments for e-skin, health monitoring, and wearable electronic devices.

CXCL12 derived from CD248-expressing cancer-associated fibroblasts mediates M2-polarized macrophages to promote nonsmall cell lung cancer progression.

Nonsmall cell lung cancer (NSCLC) is among the most prevalent malignant tumours threatening human health. In the tumour microenvironment (TME), cancer-associated fibroblasts (CAFs) induce M2-polarized macrophages, which strongly regulate tumour progression. However, little is known about the association between CAFs and M2 macrophages. CD248 is a transmembrane glycoprotein found in several cancer cells, tumour stromal cells, and pericytes. Here, we isolated CAFs from tumour tissues of NSCLC patients to detect the relationship between CD248 expression and patient prognosis. We knocked down the expression of CD248 on CAFs to detect CXCL12 secretion and macrophage polarization. We then examined the effects of CD248-expressing CAF-induced M2 macrophage polarization to promote NSCLC progression in vitro and in vivo. We found that CD248 is expressed mainly in NSCLC-derived CAFs and that the expression of CD248 correlates with poor patient prognosis. Blocking CXCL12 receptor (CXCR4) drastically decreased M2 macrophage chemotaxis. CD248 promotes CAFs secreting CXCL12 to mediate M2-polarized macrophages to promote NSCLC progression both in vitro and in vivo. Collectively, our data suggest that CD248-positive CAFs induce NSCLC progression by mediating M2-polarized macrophages.