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Abstract

Metastasis is the leading cause of death in patients with cervical cancer. In this report, we establish novel fluorescent HeLa tumor metastasis models to determine whether HeLa transfected with the enhanced red fluorescent protein (DsRed2) gene in vitro and xenotransplanted through subcutaneous, intraperitoneal, or intravenous route into SCID mice would permit the detection of tumor micro-metastasis in vivo. Our results showed that DsRed2 insertions did not interfere the tumorigenic properties of HeLa cells. We also demonstrated that DsRed2-transduced HeLa cells maintained stable high-level DsRed2 expressions during their growth in vivo. DsRed2 fluorescence clearly demarcated the primary seeding place and readily allowed for the visualization of distant micro-metastasis and local invasion at the single-cell level. Lung metastasis, the major cause of cervical carcinoma related death, was found in all three models. However, intravenous injections of the HeLa-DsRed2 cells established tumor foci in the lung, while subcutaneous and intraperitoneal injections only established lung metastasis at single-cell levels. The DsRed2 tagged HeLa cancer model allowed detection and investigation of physiologically relevant patterns of cancer invasion and metastasis in vivo.

Loss of plakoglobin promotes decreased cell-cell contact, increased invasion, and breast cancer cell dissemination in vivo

“…We first compared the expression of plakoglobin in weakly metastatic MCF7, nonmetastatic T47D, and highly metastatic HeLa, MDA-MB-436, and MDA-MB-231 cell lines [13-16,21-24]. Real-time PCR analysis showed significantly higher levels of plakoglobin in MCF7 and T47D breast cancer cells compared with HeLa, MDA-MB-231, or MDA-MB-426 ( P < 0.0001 for T47D cells and P < 0.005 for MCF7 cells compared with HeLa, MDA-MB-231, or MDA-436) (Figure 1A).…”

“…We have designed small ssRNA sequences of approximately 22 nucleotides in length that trigger gene silencing through specific cleavage and RNA degradation to target plakoglobin exclusively [11,12]. We compared the effects of reduced plakoglobin expression in weakly metastatic MCF7 and nonmetastatic T47D breast cancer cells on growth, adhesion, migration, and invasion in vitro [13-16]. In addition, we analyzed tumor growth and intravasation from the mouse mammary fat pad into the circulation in vivo .…”

Investigating Breast Cancer Cell Behavior Using Tissue Engineering Scaffolds

“…Patel et al reported a hierarchy of BCCs with the most immature subset (Oct4 hi /CD44 hi/med /CD24 -/+ ) demonstrating chemoresistance, dormancy, and stem cell properties [ 4 ]. Moreover, gene analysis revealed that these BCCs cell subtype (with CD44 + /CD24 − / claudin-low expression) also possessed higher flexibility that allowed them to change shape to pass through micro-barriers [ 4 , 5 , 91 ].…”