ORIGINAL PAPER
Effect of Increased Extracellular Ca
Production and Tumor Spheroid Formation
DOI 10.1007/s12307-010-0049-0
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Received: 19 March 2010 / Accepted: 24 June 2010
Received: 19 March 2010 / Accepted: 24 June 2010
Abstract
Research from our laboratory has demonstrated that membrane delimited
microvesicles are shed from many types of malignant
tumors, in the peripheral blood of cancer patients as well
as in culture media of tumor cells propagated in vitro
(Ginestra et al. Anticancer Res 18:3433
documented effects involve the activation of signal transduction
pathways by cellular cross-talk that are associated
with epigenetic mechanisms that may be important in tumor
progression, metastasis, and the activation of angiogenesis
(Distler et al. Arthritis Rheum 52:3337
cell imaging microscopic studies conducted in our laboratory
of the formation of solid tumor spheroids in vitro show
that the shedding of microvesicular structures from tumor
cells occurs during this process. The observed properties of
the tumor microvesicles suggest a role in solid tumor
formation and intercellular communication. The tumor
associated microvesicles were shown to be non-apoptotic
based on the absence of fluorescent nuclear staining by
acridine orange/ethidium bromide staining. Increased concentration
of extracellular Ca
increase in the production of tumor-derived microvesicles
and also to result in the formation of tumor spheroids
whose size was considerably smaller than controls.
Increased extracellular [Ca
the rapid dissociation of solid tumor spheroids to smaller
cell aggregates in the absence of significant apoptosis.

