Cancers involving the lung mediate human marrow cell phenotype change.

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10618 Background: Microvesicles from different tissues can mediate genetic phenotype changes of adjacent normal marrow cells. Methods: We have evaluated excised tissue from cancers involving the lung for their capacity to change the genetic phenotype of co cultured human marrow cells. thirteen cancers were evaluated: 11 were primary non-small cell lung cancers and there was one sarcoma and one melanoma of the lung. Excised tissue was co cultured opposite normal volunteer human bone marrow for 2 or 7 days with the cancer tissue separated from the human marrow by a cell impermeably 0.4 um membrane. Real-time RT-PCR for the following lung specific genes, aquaporin 1, aquaporin 2, aquaporin 3, aquaporin 4, aquaporin 5, surfactant A, B, C, and D, and clara cell-specific protein was carried out on 9 tumors. Results: In each instance, including the sarcoma and the melanoma, lung specific genes were highly expressed in the marrow cells. There was expression of from 1-8 lung-specific genes from different cancers ranging from over 2 fold to over 1000 fold of control. Expression was seen in co cultured whole marrow, ficol separated marrow and marrow subjected to ammonium chloride lysis. Human marrow exposed to conditioned media from lung cancer cells expressed high levels of pulmonary specific genes. Ultracentrifugation (28,000 g) of lung cancer conditioned media, pelleted large numbers of microvesicles (diameter 100-180 nm as shown by electron microscopy). Tumor-derived microvesicles also induced expression of lung-specific mRNA in target marrow cells. Pelleted microvesicles stained by the supravital dyes CFSE (green fluorescence) and PKH26 (red fluorescence) were shown to be taken up by human bone marrow cells. Conclusions: These studies indicate that cancer cells are capable of transferring a lung genetic phenotype to marrow cells. Whether this represents genetic information transferred primarily from lung to cancer cells and then secondarily to target co cultured cells or priamry genetic information from the cancer cells ia at present unknown. The capacity of cancer cells to transfer genetic phenotype suggests important possible modes of cancer progression, resurrence and metastases. It also suggests therapeutic strategies to block these occurrences. No significant financial relationships to disclose.