We also conjecture that high levels of SPP1 may prompts tumor cells invasion of the ECM into parietal pleura, proceeding to intravasation of tumor cells into the blood stream and subsequent extravasation assisted with urokinase plasminogen activator (uPA) and matrix metalloproteases (MMPs), leading to migration of neoplastic cells to form metastasis at secondary sites. Here, SPP1 is linked to neoplasm.