Fig. 4 | Nature Communications

Fig. 4

From: Radionuclides transform chemotherapeutics into phototherapeutics for precise treatment of disseminated cancer

Fig. 4

CRIT selects for CD49d cells in MM model. a Bioluminescence intensity plot showing resistant nature of MM cells extracted from treated cohort (MM1CRIT-RES) upon rechallenging with CRIT in fresh mice. b No difference in GLUT1 mRNA expression was observed between parental MM1.S cells and resistant MM1.SCRIT-RES cells as assessed by qRT-PCR. ns not significant. ch No difference in expression of CD29 was observed between MM1.S cells (c) or MM1.SCRIT-RES cells (d) following treatment with CRIT in vivo. MM1.S stopped responding to CRIT by downregulating expression of VLA-4 subunit CD49d (Resistance = 28.12% CD49d+) (f) relative to parental cells injected into mice at the beginning of the experiment (parental = 99.92% CD49d+) (e), resulting in reduced binding of the VLA-4-targeting ligand LLP2A on resistant cells (h) (LLP2A+ = 6.6%) compared to parental MM1.S (g) (LLP2A+= 84.15%). i No significant difference in colony-forming units of progenitor stem cells was observed between untreated, control and treated mice. j To determine if CRIT reduced engraftment of haematologic cells in vivo, we assessed BM repopulation following CRIT treatment. Bone marrow from treated mice or PBS-treated controls were mixed with congenic B6.CD45.1/2 at a ratio of 1:1 before infusion of 1 × 106 total BM cells into lethally irradiated (TBI 1100 cGy) B6.CD45.1 recipients. k Percentage of cells derived from treated donor BM (CD45.2) were calculated as a percentage of total donor BM (CD45.2 + CD45.1/2). BM from CRIT-treated mice effectively repopulated recipients (n = 5 per group)

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