Implanted TC-1 cells invade neighboring skeletal muscle fibers in a cancer murine model

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Adolfo Soto-Domínguez; Javier I. Vázquez-Morales; Víktor J. Romero-Díaz; Martha E. Santoyo-Pérez & Julio Sepúlveda-Saavedra

Summary

TC-1 cells implanted in C57BL/6 mice are a model for evaluation of anti-tumor immunotherapy. To date there are no reports on the effect of implanted TC-1 cells upon neighboring striated muscle cells. The objective of this work was to evaluate the morphology of the interaction established among the implanted cells and the striated muscle cells. The study was carried out as follows: 8 adult C57BL/6 mice received 5x104 cells IP. As a control, 3 mice received no cells. 10 days after cells injection, no signs of tumor are present yet, and the site of cells injection was collected for morphological studies. Samples were processed for light and transmission electron microscopy. Histological sections were stained with H & E, Masson trichromic method, PAS histochemistry and immunohistochemistry for cytocheratins AE1/AE3, muscle specific actin and for matrix metalloproteinase-9. Cross section diameter of muscle sections was compared among experimental and control groups. The histological evaluation showed groups of tumor cells, infiltrating the spaces among muscle fibers. Muscle fibers showed variations in the cross section diameter as well as in the staining pattern. TC-1 cells were seen very close to muscle cells, invading the lamina externa and sarcolema to finally form groups of cells located within the sarcoplasm. This finding was demonstrated by the specific immunolabel for each kind of cell. Reactivity for metalloproteinase- 9 was observed within the tumor cells and in the space mediating between the tumor cells and the muscle fiber. At the ultrastructural level, variations of the thickness of lamina externa were observed, as well as interruptions of this structure. Sarcolema also showed fragmentation, and close to these sites a number of subsarcolemmal vesicles were seen. In the vicinity of the muscle fiber, TC-1 cells formed membrane projections directed towards muscle membrane. Muscle fibers showed a significant diminution of cross section diameter. These findings should be considered, when utilizing this model for evaluating antitumor immunotherapy.

KEY WORDS: TC-1 cells; Intrasarcoplasmic invasion; Cancer murine model.

How to cite this article

SOTO-DOMÍNGUEZ, A.; VÁZQUEZ-MORALES, J. I; ROMERO-DÍAZ, V. J.; SANTOYO-PÉREZ, M. E. & SEPÚLVEDA- SAAVEDRA, J. Implanted TC-1 cells invade neighboring skeletal muscle fibers in a cancer murine model. Int. J. Morphol., 31(2):520- 527, 2013.