Fig 1: Blockade of CX3CL1/CX3CR1 and glutaminase inhibits SM and enhances the chemosensitivity of ER+ BC cells. (A) Representative bioluminescence imaging (BLI) imaging of each mouse group. (B) Representative micro-CT images of each group. (C) Hematoxylin and eosin (H&E) staining of each group. (D-F) Immunohistochemistry (IHC) staining for CX3CR1, GLS1, and Raptor in each group. Blank MCF-7 cells were used as the control group (a). The other groups were established with LAPTM5-sh3 (knockdown) cells, and groups (b-f) were injected with saline (b), docetaxel (c), BPTES+docetaxel (d), JMS-17-2+docetaxel (e), and BPTES+JMS-17-2+docetaxel (f). CX3CL1, C-X3-C motif chemokine ligand 1; CX3CR1, C-X3-C motif chemokine receptor 1; ER+ BC, estrogen receptor-positive breast cancer; SM, spinal metastasis; LAPTM5, lysosomal protein transmembrane 5; GLS1, glutaminase 1.
Fig 2: CX3CL1/CX3CR1 interaction mediates SM of ER+ BC cells by activating PI3K/AKT signaling to downregulate LAPTM5 expression. (A) IHC staining of CX3CR1 in ER+ BC tissue, tumor-adjacent normal tissue and SM tissue from patients and mouse models. (B and C) Quantitative analysis of the IHC results of CX3CR1. *P<0.05, **P<0.01, and ***P<0.001, compared to the normal tissues. (D) The protein level of LAPTM5 under CX3CL1 and/or the CX3CR1 inhibitor JMS-17-2 treatment. ***P<0.001, compared to untreated cells. (E) The protein level of LAPTM5 in blank and LAPTM5-OE (overexpressing) cells treated with CX3CL1 and/or the CX3CR1 inhibitor JMS-17-2. ***P<0.001, compared to untreated cells. (F) Activation of PI3K/AKT signaling and LAPTM5 expression under PBS, CX3CL1, CX3CL1+JMS-17-2, or CX3CL1+MK-2206 (AKT inhibitor) treatment. *P<0.05, **P<0.01, and ***P<0.001, compared with the untreated cells. LAPTM5, lysosomal protein transmembrane 5; ER+ BC, estrogen receptor-positive breast cancer; CX3CL1, C-X3-C motif chemokine ligand 1; CX3CR1, C-X3-C motif chemokine receptor 1; SM, spinal metastasis; p-, phosphorylated.
Fig 3: Schematic depicting the role of LAPTM5 in regulating the malignant progression and SM of ER+ BC. (A) LAPTM5 downregulation promotes the proliferation, migration, and chemoresistance of ER+ BC cells by activating glutamine-mediated mTOR signaling. (B) CX3CL1/CX3CR1 interaction mediates the vertebrae-specific inhibition of LAPTM5 and the SM of ER+ BC via PI3K/AKT signaling. LAPTM5, lysosomal protein transmembrane 5; ER+ BC, estrogen receptor-positive breast cancer; CX3CL1, C-X3-C motif chemokine ligand 1; CX3CR1, C-X3-C motif chemokine receptor 1; SM, spinal metastasis; GLS, glutaminase; S6K1, ribosomal protein S6 kinase 1; 4EBP1, eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1; MMP9, matrix metallopeptidase 9; nuclear factor κB, NFκB.
Supplier Page from MedChemExpress for Fractalkine/CX3CL1 Protein, Human (CHO)