For the study of translational tumor biology, human lung cancer cell lines are convenient but limited models as they don’t reproduce the three-dimensional cellular interactions of tumors in-vivo. Recent studies suggest the utility of primary human cancer xenografts as better models for cancer biology and therapeutics. Examples include demonstration of genetic changes such as EGFR amplification in primary brain tumors that are maintained in xenograft tumors but not in tissue cultures (Pandita, 2004); at our institution, primary pancreatic cancer xenograft lines can model preclinical responses to Hedgehog pathway inhibitors (Berman, 2004). Such xenografts usually require surgically resected samples, unlikely situation for Small Cell Lung Cancers (SCLC). We are reporting on what we believe are the first series of human SCLC xenografts grown from bronchoscopically retrieved samples, their biologic properties and preliminary translational studies.
Suspected cases of primary SCLC are confirmed by specific stains. Samples are collected either by Trans Bronchial Needle Aspiration (TBNA) of mediastinal lymph nodes or tumor masses or endobronchial tumors. In two cases, visible exophytic tumor cells are collected by physical debulking with forceps or mechanical microdebrider. Tumor cells are collected by collagenase disaggretion and subsequently injected with MatrigelTM subcutaneously into NOD/SCID mice. Subcutaneous tumors are passed into subsequent mice, or cryo-preserved and reinjected multiple times.
All five xenograft tumor cell lines show classic SCLC histology and immunohistochemical staining. Three of five subcutaneously injected tumors demonstrate organ trophism by growing as large mediastinal masses without detectable extrathoracic disease. Preliminary studies demonstrate biomarker expression of the Sonic Hedgehog pathway.
Bronchoscopically obtained samples from SCLC are successfully cultured as tumor xenografts that demonstrate typical SCLC characteristics and surprising organ trophism. These xenograft lines represent a novel and more accurate preclinical model of SCLC.
Viable SCLC xenograft models will provide mechanisms for validating SCLC biomakers, and direct pathways towards logical design and testing of targeted therapies. It may be useful as test systems of novel combination therapies, and has potential for SCLC tumor-specific vaccine development.
Rex Yung, None.