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Reporter activity and metastasis of ffLuc-eGFP-labeled cancer cells are consistent in GH mice but suppressed in immunocompetent wildtype mice.

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posted on 2014-11-04, 12:53 authored by Chi-Ping Day, John Carter, Zoe Weaver Ohler, Carrie Bonomi, Rajaa El Meskini, Philip MartinPhilip Martin, Cari Graff-Cherry, Lionel Feigenbaum, Thomas Tüting, Terry Van Dyke, Melinda Hollingshead, Glenn Merlino

A–D, Functional comparison of GH and WT mice as transplantation hosts using a breast cancer model. The GFP+ population from ffLuc-eGFP-transduced Mvt1 mouse breast cancer cells was isolated and expanded in culture. 1×105 cells were injected into the mammary fat pads (m.f.p.) of WT and GH syngeneic FVB/N mice, followed by BL imaging to monitor tumor growth. Though tumors grew in the fat pads of both groups, the BL intensity (mean ± SE) of those in WT mice was highly suppressed relative to GH mice (A). *, P = 0.083; **, P<0.001. (B–C) Upon reaching 500 mm3 m.f.p. tumors were resected, and BL imaging was used to monitor metastatic progression, which is visualized by body BL signal in each mouse. Metastatic disease progressed consistently in GH mice (B), while being suppressed in WT mice (C); the sign and number at side refer to individual mice in each figure. Kaplan-Meier survival analysis showed that GH mice exhibited significantly shorter survival times than WT mice (P = 0.0025). Median survival times in GH and WT groups were 16.5 and 41.5 days, respectively (D). E–H, Behavioral inconsistency of labeled tumors in WT and immunocompromised mice as compared to GH mice. ffLuc-eGFP-labeled LLC tumors were transplanted subcutaneously into syngeneic GH mice, strain-unmatched immunocompromised NOD/SCID (BALB/c) mice, and syngeneic c-Brd (WT) mice. Upon reaching 500 mm3 subcutaneous tumors were resected, and mice were subjected to periodic BL imaging to monitor metastasis. The growth curves representing metastatic growth in GH (E), NOD/SCID (F), and c-Brd WT mice (G) are shown; the sign and number at side refer to individual mice in each figure. Compared to those in GH mice, the metastatic growth in the other two groups exhibited heterogeneous and delayed patterns. In accordance with their more efficient metastatic progression, Kaplan-Meyer survival analysis showed that GH mice exhibited significantly shorter survival time than the other two strains of mice (P = 0.0037). Median survival times in WT, NOD/SCID, and GH groups were 18 days, 16.5 days and 11 days, respectively (H).

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