CD155/PVR plays a key role in cell motility during tumor cell invasion and migration

BACKGROUND: Invasion is an important early step of cancer metastasis that is not well understood. Developing therapeutics to limit metastasis requires the identification and validation of candidate proteins necessary for invasion and migration. METHODS: We developed a functional proteomic screen to identify mediators of tumor cell invasion. This screen couples Fluorophore Assisted Light Inactivation (FALI) to a scFv antibody library to systematically inactivate surface proteins expressed by human fibrosarcoma cells followed by a high-throughput assessment of transwell invasion. RESULTS: Using this screen, we have identified CD155 (the poliovirus receptor) as a mediator of tumor cell invasion through its role in migration. Knockdown of CD155 by FALI or by RNAi resulted in a significant decrease in transwell migration of HT1080 fibrosarcoma cells towards a serum chemoattractant. CD155 was found to be highly expressed in multiple cancer cell lines and primary tumors including glioblastoma (GBM). Knockdown of CD155 also decreased migration of U87MG GBM cells. CD155 is recruited to the leading edge of migrating cells where it colocalizes with actin and αv-integrin, known mediators of motility and adhesion. Knockdown of CD155 also altered cellular morphology, resulting in cells that were larger and more elongated than controls when plated on a Matrigel substrate. CONCLUSION: These results implicate a role for CD155 in mediating tumor cell invasion and migration and suggest that CD155 may contribute to tumorigenesis

The embodied listener: a dyadic case study of how therapist and patient reflect on the significance of therapist`s personal presence for the therapeutic change process

Objective: There is a need to understand more of the dyadic processes in therapy and how the therapist’s ways of being are experienced and reflected upon by both patient and therapist. The aim of this dyadic case study was to investigate how the therapist’s personal presence was perceived by the patient and the therapist as contributing to change. Method: From a larger project on collaborative actions between patient and therapist, a dyadic case involving in-depth interviews of the therapist and patient was selected to examine the research question. Interpretative phenomenological analysis of four interviews with the therapist and one interview with the patient was conducted. Results: The analyses indicated that the therapist’s way of being, as perceived by both therapist and patient, was expressed at a superordinate level through the concept of embodied listening, which was of particular help for the patient, and influenced by the therapist’s theoretical orientation, as well as being rooted in his own personal history. Three sub-themes emerged from the analysis, each illustrating how embodied listening contributed to the therapeutic relationship and process. Our findings flesh out how the underlying phenomena of emotional attunement, presence, and genuineness are observable in therapeutic encounters

"It's both a strength and a drawback." How therapists' personal qualities are experienced in their professional work

Objective: The aim of this study was to gain knowledge about how the integration of personal and professional experiences affects therapeutic work. Method: Therapists (N = 14) who had been recommended by their leaders at their individual workplaces were interviewed twice with semi-structured qualitative interviews, which were then subjected to thematic and Interpretative Phenomenological Analysis. Results: All the therapists in the sample described their personal qualities as an experienced tension between their personal strengths and vulnerabilities in the therapeutic setting. This tension came to expression through four subordinate themes: (a) The tension between perceiving oneself as a helper while dealing with one’s own needs for attention and care; (b) The tension between the ability for embodied listening to the patient while tuning into oneself; (c) The tension between staying present while handling aggression and rejection from clients; and (d) The tension in striving for a constructive balance between closeness and distance. Conclusion: The results point to ways in which the personal selves of the therapists may affect their professional role performance. Drawing upon previous research and literature on the topic, the paper discusses how therapists’ personal qualities are experienced as affecting their work and suggests several implications for psychotherapy training and practice

How psychotherapists make use of their experiences from being a client: Lessons from a collective autoethnography

First-hand experience of being a client is regarded by many psychotherapists as making an essential contribution to professional development. Although research has not established any direct influence on client outcome, arising from therapist participation in personal therapy, qualitative studies have explored how therapists transfer learning from one context to the other. A group of six therapists-researchers engaged in a collective autoethnography in which we shared narrative accounts of our own experiences as clients. Together we covered a wide set of therapies, sought for varied purposes, and from different stages in the life-course. Different areas of learning were identified: negative experiences could strengthen own convictions for acting differently; positive experiences worked as inspiration and support; being in therapy early in life represented a significant formative experience; working through complex personal issues in therapy gave the courage to identify similar conflicts in phantasies and realities of clients. The link between having been a client and working as a therapist is a subjective, reflective process of reworking figure and ground in the search for professional sensitivity

A Host-Specific, Temperature-Sensitive Translation Defect Determines the Attenuation Phenotype of a Human Rhinovirus/Poliovirus Chimera, PV1(RIPO) ▿

By using a rhinosvirus/poliovirus type 1 chimera, PV1(RIPO), with the cognate internal ribosome entry site (IRES) of human rhinovirus type 2 (HRV2), we set out to shed light on the mechanism by which this variant expresses its attenuated phenotype in poliovirus-sensitive, CD155 transgenic (tg) mice and cynomolgus monkeys. Here we report that replication of PV1(RIPO) is restricted not only in human cells of neuronal origin, as was reported previously, but also in cells of murine origin at physiological temperature. This block in replication was enhanced at 39.5°C but, remarkably, it was absent at 33°C. PV1(RIPO) variants that overcame the replication block were derived by serial passage under restrictive conditions in either mouse cells or human neuronal cells. All adapting mutations mapped to the 5′-nontranslated region of PV1(RIPO). Variants selected in mouse cells, but not in human neuronal cells, exhibited increased mouse neurovirulence in vivo. The observed strong mouse-specific defect of PV1(RIPO) at nonpermissive temperature correlated with the translational activity of the HRV2 IRES in this chimeric virus. These unexpected results must be kept in mind when poliovirus variants are tested in CD155 tg mice for their neurovirulent potential, particularly in assays of live attenuated oral poliovirus vaccine lots. Virulence may be masked by adverse species-specific conditions in mouse cells that may not allow accurate prediction of neurovirulence in the human host. Thus, novel poliovirus variants in line for possible development of human vaccines must be tested in nonhuman primates