Berkeley Lab researchers discover critical rotational motion in cells
Image courtesy of Berkeley Lab
Photo by Roy Kaltschmidt, Berkeley Lab
"In addition to wanting to know how a single cell and its progeny assemble into polar tissue, we also wanted to know whether cellular dynamics are corrupted by malignant transformation," Bissell says. "In this study, we found that malignant cells do not display CAMo but instead become randomly motile and do not form spheres."
In recent research, Bissell and her group demonstrated that through manipulation of the ECM, malignant cells cultured in an ECM enriched with laminin – a protein that they had shown induces cell quiescence - can undergo a reversion in which their normal phenotype is restored despite their malignant genome. In this new study, Tanner, Bissell and their colleagues found that when malignant cells cultured in the 3D ECM surrogate gel underwent phenotypic reversion in response to signaling inhibitors, CAMo was restored. When CAMo was restored, the reverted cancer cells formed polarized spheres.
"These results complement our early hypothesis that signaling and support by the ECM when cells are in proper context informs both form and function in cells," Bissell says. "The results also suggest that in response to microenvironmental cues from the ECM, cells execute a program of cytoskeletal movements that dictate different kinds of motilities. We hypothesize that these motilities direct the formation of a given type of tissue and preclude other multicellular geometries. We believe this is a crucial evolutionary phenomena for multicellular organisms."
In this new study, Tanner and Bissell and their colleagues were surprised to observe a significant delay between the second and third round of breast cell divisions in the 3D ECM surrogate gel. This mitotic delay is similar to the mitotic delay that's been observed during human blastocyst formation and is critical for normal embryogenesis. Tanner says the delay is probably necessary for the progeny to acquire sufficient adhesion so that the CAMo can be maintained for the adhere cells. This finding may provide a possible explanation for how the mammary gland reorganizes after each pregnancy and involution.
"Once the cells are sufficiently adhered to one another, they can continue CAMo as a cohesive unit," Tanner says. "We postulate that this cohesive CAMo motility is the mechanism by which the original structure of the breast tissue is restored following lactation and breast feeding."
The next step for the research team will be to study the effects of CAMo from the perspective of the ECM.
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