Immunoglobulin superfamily containing leucine-rich repeat protein (ISLR) (ISLR)

Meflin, also known as Immunoglobulin superfamily containing leucine-rich repeat protein (ISLR), is a glycosylphosphatidylinositol (GPI)-anchored membrane protein that serves as a specific marker for mesenchymal stromal/stem cells (MSCs) and a subset of cancer-associated fibroblasts (CAFs) known as cancer-restraining fibroblasts (rCAFs). It plays a critical role in maintaining the undifferentiated state of MSCs and modulating the tumor microenvironment by inhibiting lysyl oxidase (LOX) activity, which prevents the stiffening of the extracellular matrix that typically promotes cancer progression and drug resistance. Additionally, Meflin augments bone morphogenetic protein 7 (BMP7) signaling, which counteracts the pro-tumorigenic and pro-fibrotic effects of TGF-beta. In clinical contexts, high stromal Meflin expression is a favorable prognostic biomarker in pancreatic and lung cancers, correlating with improved survival and enhanced sensitivity to immune checkpoint inhibitors. Conversely, Meflin is upregulated in chemoresistant osteosarcoma cells, where it contributes to stem-like properties and tumorigenicity, making it a promising target for antibody-drug conjugates (ADCs). Therapeutic strategies currently focus on either inducing Meflin expression using agents like Vitamin D to normalize the tumor stroma or directly targeting Meflin-positive malignant cells with ADCs to overcome refractory disease.

Other names

MeflinMesenchymal stromal cell- and fibroblast-expressing Linx paralogueHsT17563

Antibody-drug conjugates (ADCs) target Meflin-positive malignant cells to deliver cytotoxic payloads, while Vitamin D acts as an inducer to increase Meflin expression in cancer-associated fibroblasts, thereby reprogramming the tumor stroma from a promoting to a restraining state.