Ovarian cancer (OvCa) exhibits a specific predilection for metastasis to the omentum. Our earlier studies highlighted the tumour-suppressor effect of secreted protein acidic and rich in cysteine (SPARC) in OvCa through multi-faceted roles inhibiting cancer cell interactions within the peritoneal milieu. The goal of this study is to investigate the role of SPARC in OvCa interactions with omental adipocytes and its role in OvCa colonization in the omentum. We employed multi-pronged approach using primary omental adipocytes from Sparc knockout mice, genetically engineered human omental adipocytes in 3D co-cultures with OvCa cells, as well as treatment with recombinant SPARC protein. We show that SPARC suppresses multistep cascade in OvCa omental metastasis. SPARC inhibited in vivo and adipocyte-induced homing, proliferation, and invasion of OvCa cells. SPARC suppressed metabolic programming of both adipocytes and OvCa cells and exerted an inhibitory effect of adipocyte differentiation and their phenotypic switch to cancer-associated phenotype. Mechanistic studies revealed that this effect is mediated through inhibition of cEBPβ-NFkB-AP-1 transcription machinery. These findings define a novel and functionally important role of SPARC in OvCa and not only bridge the knowledge gap but highlight the need to consider SPARC protein expression in therapeutic development.
Ovarian cancer is the fifth most common cancer affecting the female population and at present, stands as the most lethal gynecologic malignancy. Poor prognosis and low five-year survival rate are attributed to nonspecific symptoms and below par diagnostic criteria at early phases along with a lack of effective treatment at advanced stages. It is thus of utmost importance to understand ovarian carcinoma through several lenses including its molecular pathogenesis, epidemiology, histological subtypes, hereditary factors, diagnostic approaches and methods of treatment. Above all, it is crucial to dissect the role that the unique peritoneal tumor microenvironment plays in ovarian cancer progression and metastasis. This review seeks to highlight several important aspects of ovarian cancer pathobiology as a means to provide the necessary background to approach ovarian malignancies in the future.
Ovarian cancer is the fifth most common cancer affecting women and at present, stands as the most lethal gynecologic malignancy. The poor disease outcome is due to the nonspecific symptoms and the lack of effective treatment at advanced stages. Thus, it is of utmost importance to understand ovarian carcinoma through several lenses and to dissect the role that the unique peritoneal tumor microenvironment plays in ovarian cancer progression and metastasis. This review seeks to highlight several determinants of this unique tumor microenvironment, their influence on disease outcome and ongoing clinical trials targeting these determinants.
Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm with uncertain histogenesis. Most cases behave in a clinically benign fashion; however, a small percentage of tumors may locally recur or metastasize. Herein we present a case of a 56-year-old man who presented with an enlarging left groin mass, left inner thigh numbness, burning paresthesia and discomfort in his left groin. The mass sampled by fine- needle aspiration and needle core biopsy. Cytology showed bland-appearing epithelioid cells with round nuclei and fine chromatin, with fragments of fibromyxoid stroma in the background. Immunohistochemical stains performed on the core biopsy showed that the lesional cells were focally positive for S100 protein and negative for desmin, smooth muscle actin, CD34 and cytokeratin AE1/AE3. A benign neoplasm was favored with ossifying fibromyxoid tumor as the main entity in the differential diagnosis. A subsequent resection showed a well-circumscribed 5 cm mass with firm consistency and focal areas of calcifications. Histologically, the tumor had a nodular growth pattern with relatively bland spindle cells containing round to oval nuclei suspended in a variably collagenous to myxoid stroma. Significant ossification and bone formation was also noted. There was no significant atypia, necrosis or increased mitoses. Ossifying fibromyxoid tumors have distinct cytologic features and should be considered in the differential diagnosis of soft tissue tumors with prominent ossification.
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