A Model of Lymphangioleiomyomatosis in a Three-Dimensional Culture System
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Published on: March 17, 2020
Toshio Kumasaka1,2, Yoshito Hoshika3,2, Etsuko Kobayashi3,2
11 Department of Pathology, Japanese Red Cross Medical Center , Tokyo, Japan .
Background:
Lymphangioleiomyomatosis (LAM) is a tumor consisting of benign-looking neoplastic cells, but its wretched clinical outcome often resembles a malignant disease. LAM cell clusters (LCCs), unique microstructures commonly found in LAM-associated chylous effusion, are aggregates of LAM cells rimmed by lymphatic endothelium. LCCs seem to be crucial participants in the dissemination and progression of LAM.
Methods And Results:
LCCs isolated from LAM-associated chylous effusion were embedded in a three-dimensional (3-D) culture gels, and then placed in a humidified CO2 incubator. During serial observations of their morphological changes, we found tube formations with lymphatic endothelial cells when LCCs settled side by side in 3-D gels. On the other hand, when LCCs were embedded separately enough to be isolated at their initial sites of settlement in the gels, each of LCCs gradually broke down, leaving a "cyst-like" hole after 7 days at the site where LCCs initially resided. Finally, we demonstrated that "cyst-like" hole formation in 3-D gels was inhibited with treatment with doxycycline or recombinant human VEGF receptor-3.
Conclusions:
We consider that our observation of this sequence in vitro illustrates how LCCs behave in vivo while enacting their important role in the progression of LAM. Our results indicate that the 3-D gel culture system for LCCs is a useful tool for exploring the effects of new therapeutic drugs under conditions when LCCs are constantly available.
