Asymmetrical positioning of cell organelles reflects the cell chirality of mouse myoblast cells.

Cell chirality is crucial for the chiral morphogenesis of biological tissues, yet its underlying mechanism remains unclear. Cell organelle polarization along multiple axes in a cell body, namely, apical-basal, front-rear, and left-right, is known to direct cell behavior such as orientation, rotation, and migration. Among these axes, the left-right bias holds significant sway in determining the chiral directionality of these behaviors. Normally, mouse myoblast (C2C12) cells exhibit a strong counterclockwise chirality on a ring-shaped micropattern, whereas they display a clockwise dominant chirality under Latrunculin A treatment. To investigate the relationship between multicellular chirality and organelle positioning in single cells, we studied the left-right positioning of cell organelles under distinct cell chirality in single cells via micropatterning technique, fluorescent microscopy, and imaging analysis. We found that on a "T"-shaped micropattern, a C2C12 cell adopts a triangular shape, with its nucleus-centrosome axis pointing toward the top-right direction of the "T." Several other organelles, including the Golgi apparatus, lysosomes, actin filaments, and microtubules, showed a preference to polarize on one side of the axis, indicating the universality of the left-right asymmetrical organelle positioning. Interestingly, upon reversing cell chirality with Latrunculin A, the organelles correspondingly reversed their left-right positioning bias, as suggested by the consistently biased metabolism and contractile properties at the leading edge. This left-right asymmetry in organelle positioning may help predict cell migration direction and serve as a potential marker for identifying cell chirality in biological models.

Heparan Sulfate Modulation Affects Breast Cancer Cell Adhesion and Transmigration across In Vitro Blood-Brain Barrier.

The disruption of endothelial heparan sulfate (HS) is an early event in tumor cell metastasis across vascular barriers, and the reinforcement of endothelial HS reduces tumor cell adhesion to endothelium. Our recent study showed that while vascular endothelial growth factor (VEGF) greatly reduces HS at an in vitro blood-brain barrier (BBB) formed by human cerebral microvascular endothelial cells (hCMECs), it significantly enhances HS on a breast cancer cell, MDA-MB-231 (MB231). Here, we tested that this differential effect of VEGF on the HS favors MB231 adhesion and transmigration. We also tested if agents that enhance endothelial HS may affect the HS of MB231 and reduce its adhesion and transmigration. To test these hypotheses, we generated an in vitro BBB by culturing hCMECs on either a glass-bottom dish or a Transwell filter. We first quantified the HS of the BBB and MB231 after treatment with VEGF and endothelial HS-enhancing agents and then quantified the adhesion and transmigration of MB231 across the BBB after pretreatment with these agents. Our results demonstrated that the reduced/enhanced BBB HS and enhanced/reduced MB231 HS increase/decrease MB231 adhesion to and transmigration across the BBB. Our findings suggest a therapeutic intervention by targeting the HS-mediated breast cancer brain metastasis.

Psychosocial consequences of false-positive results in screening mammography.

INTRODUCTION: To evaluate the psychosocial impact of benign breast biopsies on Lebanese women after a screening mammography and the effect of these biopsies on patients' attitudes toward subsequent screening. METHODS: In this retrospective study (January 2005 till April 2011), 109 consecutive patients with a history of breast biopsy without cancer were asked to answer a phone questionnaire. The response rate was 91.7% (100 women accepted to participate). A questionnaire about sociodemographic characteristics, biopsy characteristics, and patients' attitudes as measured by the negative Psychosocial Consequences Questionnaire (PCQ) and other independent questions was filled by phone call by one interviewer. RESULTS: The negative PCQ score was low for most women (only 9% have a negative PCQ score ≥18/36) and is statistically dependent on the result of the last mammography (P = 0.01) and the number of previous benign breast biopsies (P = 0.01). A total of 10% of women increased their medical visits after this biopsy, 8% were treated for psychiatric problems after this biopsy, and 19% self-examine their breasts more than once per week. The benign breast biopsy experience increases the willingness to adhere to the screening mammography in 71% of the patients, this reported adherence depends positively on the score of the negative PCQ (P = 0.043). CONCLUSIONS: The negative psychosocial effect of the biopsy is minimal in general and is positively correlated to the adherence to future mammographies. Interventions are necessary to decrease the anxiety in most susceptible women and to raise the awareness of women at risk of nonadherence to the screening mammography.