ABSTRACT
Locally advanced breast cancer (tumor > 5 cm, widespread infiltration of the skin and muscle, or metastases to lymph nodes) is difficult to resect by surgery, and even when it is resectable, there is a high probability of local recurrence and distant metastasis. Therefore, systemic therapy should be administered first. However, as cutaneous infiltration progresses, the patient's quality of life is impaired by pain, bleeding, presence of exudates, and a foulsmelling odor. Treatment with Mohs paste with systemic therapy can control symptoms associated with skin infiltration and can also be expected to decrease tumor volume.Herein, we report a case in which a tumor was resected following Mohs paste and systemic chemotherapy administration, and the skin defect was reconstructed with a latissimus dorsi myocutaneous flap. We also review the literature for previously reported cases of breast cancer involving Mohs paste.
ABSTRACT
LR11, also known as SorLA or SORL1, is a type-I membrane protein from which a large extracellular part, soluble LR11 (sLR11), is released by proteolytic shedding on cleavage with a disintegrin and metalloproteinase 17 (ADAM17). A shedding mechanism is presumed to have a key role in the functions of LR11, but the evidence for this has not yet been demonstrated. Tetraspanin CD9 has been recently shown to regulate the ADAM17-mediated shedding of tumor necrosis factor-alpha and intercellular adhesion molecule-1 on the cell surface. Here, we investigated the role of CD9 on the shedding of LR11 in leukocytes. LR11 was not expressed in THP-1 monocytes, but it was expressed and released in phorbol 12-myristate 13-acetate (PMA)-induced THP-1 macrophages (PMA/THP-1). Confocal microscopy showed colocalization of LR11 and CD9 proteins on the cell surface of PMA/THP-1. Ectopic neo-expression of CD9 in CCRF-SB cells, which are LR11-positive and CD9-negative, reduced the amount of sLR11 released from the cells. In contrast, incubation of LR11-transfected THP-1 cells with neutralizing anti-CD9 monoclonal antibodies increased the amount of sLR11 released from the cells. Likewise, the PMA-stimulated release of sLR11 increased in THP-1 cells transfected with CD9-targeted shRNAs, which was negated by treatment with the metalloproteinase inhibitor GM6001. These results suggest that the tetraspanin CD9 modulates the ADAM17-mediated shedding of LR11 in various leukemia cell lines and that the association between LR11 and CD9 on the cell surface has an important role in the ADAM17-mediated shedding mechanism.