Multicellular tumor spheroids, an in vitro 3-D model that simulates malignant-cell contacts within a tumor, can be used to evaluate tumor response to therapeutic agents. We found that MELN (derived from MCF-7 cells) cells grown in 3-D as spheroids, remain highly sensitive to estradiol in terms of growth, down-regulation of ERalpha expression and ERalpha-induced transcriptional activity. Estradi...

The purpose of this study was to establish the effect of hypoxia-inducible factor-1 (HIF-1) directly on tumor growth, independently of angiogenesis. This was done by growing wild-type mouse hepatoma cells (HEPA-1) and their HIF-1-deficient counterpart C4 as multicellular tumor spheroids and quantifying differences in growth rates and proliferative and apoptotic indices. Insulin and insulin-like...

Various in vivo studies demonstrated a migration tendency of neural stem cells (NSCs) toward gliomas, making these cells a potential carrier for delivery of therapeutic genes to disseminated glioma cells. We analyzed which factors determine NSC migration and invasion in vitro. Conditioned media prepared from 10 different human glioma cell lines, as well as 13 different tumor-associated growth f...

The limited translational value in clinic of analyses performed on 2-D cell cultures has prompted a shift toward the generation of 3-dimensional (3-D) multicellular systems. Here we present a spontaneously-forming in vitro cancer spheroid model, referred to as spheroids(MARY-X), that precisely reflects the pathophysiological features commonly found in tumor tissues and the lymphovascular embolu...

Yuhas and Li (Cancer Res., 38: 1528-1532, 1978) have proposed a method for estimating the thickness of the growing layer in multicellular tumor spheroids. Their method assumes, however, that the thickness of the growing layer is independent of spheroid radius; this assumption seems implausible in view of the fact that, for purely geometrical reasons, oxygen diffusion distance is greater in smal...

Multicellular tumor spheroids represent a 3D in vitro model that mimics solid tumor essential properties including assembly and development of extracellular matrix and nutrient, oxygen and proliferation gradients. In the present study, we analyze the impact of 3D spatial organization of HER2-overexpressing breast cancer cells on the response to Trastuzumab. We cultured human mammary adenocarcin...

Tumor microenvironments present significant barriers to penetration by antibodies and immunoconjugates and are difficult to study in vitro. Cells cultured as monolayers typically exhibit less resistance to therapy than those grown in vivo. Therefore, it is important to develop an alternative research model that better represents in vivo tumors. We have developed a protocol to produce multicellu...

Volvox rousseletii is a multicellular spheroidal green alga containing ∼5,000 cells, each equipped with two flagella (cilia). This organism shows striking photobehavior without any known intercellular communication. To help understand how the behavior of flagella is regulated, we developed a method to extract the whole organism with detergent and reactivate its flagellar motility. Upon addition...

A calcitonin (CT)-producing cell line (DMS53) established from human small cell carcinoma of the lung was grown as three-dimensional multicellular spheroids in spinner culture or on agar in multiwells, and as tumors in nude (athymic) mice. CT release into the media was directly proportional to spheroid volume. The response of these cells following exposures to X-irradiation, Adriamycin, or diaz...

The surrounding microenvironment limits tumour expansion, imposing a compressive stress on the tumour, but little is known how pressure propagates inside the tumour. Here we present non-destructive cell-like microsensors to locally quantify mechanical stress distribution in three-dimensional tissue. Our sensors are polyacrylamide microbeads of well-defined elasticity, size and surface coating t...