Deregulation of miR-27a may contribute to canine fibroblast activation after coculture with a mast cell tumour cell line.

The tumour microenvironment comprises a diverse range of cells, including fibroblasts, immune cells and endothelial cells, along with extracellular matrix. In particular, fibroblasts are of significant interest as these cells are reprogrammed during tumorigenesis to become cancer-associated fibroblasts (CAFs), which in turn support cancer cell growth. MicroRNAs (miRNAs) have been shown to be involved in this intercellular crosstalk in humans. To assess whether miRNAs are also involved in the activation of fibroblasts in dogs, we cocultured primary canine skin fibroblasts with the canine mast cell tumour cell line C2 directly or with C2-derived exosomes, and measured differential abundance of selected miRNAs. Expression of the CAF markers alpha-smooth muscle actin (ACTA2) and stanniocalcin 1 confirmed the activation of our fibroblasts after coculture. We show that fibroblasts displayed significant downregulation of miR-27a and let-7 family members. These changes correlated with significant upregulation of predicted target mRNAs. Furthermore, RNA interference knockdown of miR-27a revealed that cyclin G1 (CCNG1) exhibited negative correlation at the mRNA and protein level, suggesting that CCNG1 is a target of miR-27a in canine fibroblasts and involved in their activation. Importantly, miR-27a knockdown itself resulted in fibroblast activation, as demonstrated by the formation of ACTA2 filaments. In addition, interleukin-6 (IL-6) was strongly induced in our fibroblasts when cocultured, indicating potential reciprocal signalling. Taken together, our findings are consistent with canine fibroblasts being reprogrammed into CAFs to further support cancer development and that downregulation of miR-27a may play an important role in the tumour-microenvironment crosstalk.

Mastocitoma solitario: hallazgo en un examen de salud / Solitary mastocytoma: found in a health examination

Introducción. El mastocitoma solitario consiste en la infiltración localizada de mastocitos en la piel, y normalmente se manifiesta como una placa o mácula marronosa-anaranjada. Es una de las formas de mastocitosis más frecuente en la infancia, junto con la urticaria pigmentosa. El 55% de los casos de mastocitosis se presentan durante los 2 primeros años de vida. Observación clínica. Se presenta el caso de un niño de 18 meses que presenta una lesión de un centímetro de diámetro en región lumbar, asintomática, de meses de evolución. Al frotar la lesión, ésta se vuelve más eritematosa, y provoca molestias al paciente. Por estas características clínicas se diagnostica de mastocitoma solitario. Comentarios. El diagnóstico de mastocitoma solitario es principalmente clínico. En general no requiere tratamiento, ya que suele involucionar espontáneamente durante la edad infantil. Tan sólo en algunos casos, en los que la liberación de histamina provoca clínica sistémica, es necesario tratamiento antihistamínico(AU)

Introduction. Solitary mastocytoma consists of the localised leaking of mastocytes into the skin, and normally is manifested as a brownish- orange plaque or macule. It is one of the most frequent forms of mastocytosis in childhood, along with urticaria pigmentosa. 55% of the cases of mastocytosis appear during the first two years of life. Clinical observation. There is the case of an 18-month-old child who presents with a skin lesion that is one centimetre in diameter, in the lumbar region, asymptomatic, with some months of evolution. When the lesion is rubbed, it turns more erythematic, and bothers the patient. With these clinical characteristics, solitary mastocytoma is diagnosed. Comments. The diagnosis of solitary mastocytoma is mainly clinical. In general it doesn’t require treatment, as it normally resolves itself spontaneously during the childhood years. Only in some cases, when the secretion of histamine when the injury is rubbed causes systemic clinical symptoms, antihistaminic treatment must be established(AU)

A solitary mastocytoma presenting with urticaria and angioedema in a 14-year-old boy.

Urticaria with angioedema is a common clinical presentation that often poses a challenge for allergists. The differential diagnosis for urticaria is broad, making the evaluation and pinpointing the underlying cause difficult and frustrating for both families and physicians. Certain causes of urticaria such as infections or medications are more common and easier to identify whereas less frequently seen conditions are often overlooked because of their rarity. One such condition is mastocytosis. Mastocytosis is a rare disease that very seldom presents with urticaria but may be associated with significant morbidity and mortality if not recognized in a timely manner. We are presenting a case of a 14-year-old boy who presented with urticaria and angioedema possibly caused by a solitary mastocytoma. The learning points from this case are that mastocytosis should be considered in the differential diagnosis of urticaria and solitary mastocytomas may remain active into adolescence, raising concern for systemic progression.